Unobtrusive active eye interrogation

ABSTRACT

Methods and systems for determining a physiological parameter of a subject through interrogation of an eye of the subject with an optical signal are described. Interrogation is performed unobtrusively. The physiological parameter is determined from a signal sensed from the eye of a subject when the eye of the subject is properly aligned with regard to an interrogation signal source and/or response signal sensor.

If an Application Data Sheet (ADS) has been filed on the filing date ofthis application, it is incorporated by reference herein. Anyapplications claimed on the ADS for priority under 35 U.S.C. §§119, 120,121, or 365(c), and any and all parent, grandparent, great-grandparent,etc. applications of such applications, are also incorporated byreference, including any priority claims made in those applications andany material incorporated by reference, to the extent such subjectmatter is not inconsistent herewith.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and/or claims the benefit of theearliest available effective filing date(s) from the following listedapplication(s) (the “Priority Applications”), if any, listed below(e.g., claims earliest available priority dates for other thanprovisional patent applications or claims benefits under 35 USC §119(e)for provisional patent applications, for any and all parent,grandparent, great-grandparent, etc. applications of the PriorityApplication(s)). In addition, the present application is related to the“Related Applications,” if any, listed below.

PRIORITY APPLICATIONS

None.

RELATED APPLICATIONS

U.S. patent application Ser. No. 13/711,445, entitled SELF-ALIGNINGUNOBTRUSIVE ACTIVE EYE INTERROGATION naming ALLEN L. BROWN, DOUGLAS C.BURGER, ERIC HORVITZ, RODERICK A. HYDE, EDWARD K. Y. JUNG, ERIC C.LEUTHARDT, JORDIN T. KARE, CHRIS DEMETRIOS KARKANIAS, JOHN L.MANFERDELLI, CRAIG J. MUNDIE, NATHAN P. MYHRVOLD, BARNEY PELL, CLARENCET. TEGREENE, WILLARD H. WATTENBURG, CHARLES WHITMER, LOWELL L. WOOD,Jr., AND RICHARD N. ZARE as inventors, filed 11 Dec. 2012, is related tothe present application.

U.S. patent application Ser. No. 13/711,453, entitled TIME-BASEDUNOBTRUSIVE ACTIVE EYE INTERROGATION naming ALLEN L. BROWN, DOUGLAS C.BURGER, ERIC HORVITZ, RODERICK A. HYDE, EDWARD K. Y. JUNG, ERIC C.LEUTHARDT, JORDIN T. KARE, CHRIS DEMETRIOS KARKANIAS, JOHN L.MANFERDELLI, CRAIG J. MUNDIE, NATHAN P. MYHRVOLD, BARNEY PELL, CLARENCET. TEGREENE, WILLARD H. WATTENBURG, CHARLES WHITMER, LOWELL L. WOOD,Jr., AND RICHARD N. ZARE as inventors, filed 11 Dec. 2012, is related tothe present application.

U.S. patent application Ser. No. 13/711,459, entitled UNOBTRUSIVE ACTIVEEYE INTERROGATION WITH GAZE ATTRACTOR naming ALLEN L. BROWN, DOUGLAS C.BURGER, ERIC HORVITZ, RODERICK A. HYDE, EDWARD K. Y. JUNG, ERIC C.LEUTHARDT, JORDIN T. KARE, CHRIS DEMETRIOS KARKANIAS, JOHN L.MANFERDELLI, CRAIG J. MUNDIE, NATHAN P. MYHRVOLD, BARNEY PELL, CLARENCET. TEGREENE, WILLARD H. WATTENBURG, CHARLES WHITMER, LOWELL L. WOOD,Jr., AND RICHARD N. ZARE as inventors, filed 11 Dec. 2012, is related tothe present application.

The United States Patent Office (USPTO) has published a notice to theeffect that the USPTO's computer programs require that patent applicantsreference both a serial number and indicate whether an application is acontinuation, continuation-in-part, or divisional of a parentapplication. Stephen G. Kunin, Benefit of Prior-Filed Application, USPTOOfficial Gazette Mar. 18, 2003. The USPTO further has provided forms forthe Application Data Sheet which allow automatic loading ofbibliographic data but which require identification of each applicationas a continuation, continuation-in-part, or divisional of a parentapplication. The present Applicant Entity (hereinafter “Applicant”) hasprovided above a specific reference to the application(s) from whichpriority is being claimed as recited by statute. Applicant understandsthat the statute is unambiguous in its specific reference language anddoes not require either a serial number or any characterization, such as“continuation” or “continuation-in-part,” for claiming priority to U.S.patent applications. Notwithstanding the foregoing, Applicantunderstands that the USPTO's computer programs have certain data entryrequirements, and hence Applicant has provided designation(s) of arelationship between the present application and its parentapplication(s) as set forth above and in any ADS filed in thisapplication, but expressly points out that such designation(s) are notto be construed in any way as any type of commentary and/or admission asto whether or not the present application contains any new matter inaddition to the matter of its parent application(s).

To the extent that the listings of applications provided above may beinconsistent with the listings provided via an ADS, it is the intent ofthe Application to claim priority to all applications listed in thePriority Applications section of either document.

All subject matter of the Priority Applications and the RelatedApplications and of any and all parent, grandparent, great-grandparent,etc. applications of the Priority Applications and the RelatedApplications, including any priority claims, is incorporated herein byreference to the extent such subject matter is not inconsistentherewith.

SUMMARY

In one aspect, a system for sensing information from an eye of a subjectincludes, but is not limited to a gaze signal sensor adapted forreceiving a gaze signal containing information indicative of a gazedirection of an eye of the subject; an interrogation signal source fordelivering an interrogation signal to an eye of a subject; a responsesignal sensor for sensing a response signal produced by the eye of thesubject responsive to the interrogation signal; signal processingcircuitry including: a gaze signal processor configured to determine thegaze direction of the eye of the subject based upon the gaze signal; analignment detector configured to determine whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the gaze direction; and a response signal processorconfigured to process the response signal sensed from the eye of thesubject by the response signal sensor when the eye of the subject is inalignment with respect to the at least one of the interrogation signalsource and the response signal sensor to determine a physiologicalparameter from the response signal. In addition to the foregoing, othersystem aspects are described in the claims, drawings, and text forming apart of the disclosure set forth herein.

In one aspect, a system for controlling the sensing of information froman eye of a subject includes, but is not limited to signal processingcircuitry including: a gaze signal input adapted to receive a gazesignal containing information indicative of a gaze direction of the eyeof the subject sensed from at least an eye of the subject; a responsesignal input adapted to receive a response signal sensed from the eye ofthe subject by a response signal sensor responsive to delivery of aninterrogation signal to the eye of the subject; a gaze signal processorconfigured to determine the gaze direction of the eye of the subjectbased upon the gaze signal; an alignment detector configured todetermine whether the eye of the subject is in alignment with respect toat least one of the interrogation signal source and the response signalsensor based at least in part upon the gaze direction; and a responsesignal processor configured to process the response signal sensed fromthe eye of the subject by the response signal sensor when the eye of thesubject is in alignment with respect to the at least one of theinterrogation signal source and the response signal sensor to determinea physiological parameter from the response signal. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system includes, but is not limited to a housing; aninterrogation signal source housed in the housing and adapted fordelivering an interrogation signal to an eye of a subject, theinterrogation signal source including at least one light source and atleast one optical system; a response signal sensor housed within thehousing and adapted for sensing a response signal produced by the eye ofthe subject responsive to the interrogation signal, the response signalcontaining information regarding a physiological parameter of thesubject; an output structure adapted for transmitting an output signal;mounting means adapted for mounting the housing with respect to adisplay in such a manner that the interrogation signal source andresponse signal sensor are alignable with the eye of the subject duringnormal use of the display by the subject. In addition to the foregoing,other system aspects are described in the claims, drawings, and textforming a part of the disclosure set forth herein.

In one aspect, a method of measuring information from an eye of asubject includes, but is not limited to; delivering an interrogationsignal to the eye of the subject with an interrogation signal source;detecting a response signal from the eye of the subject with a responsesignal sensor; determining whether the eye of the subject is inalignment with respect to at least one of the interrogation signalsource and the response signal sensor; and determining a physiologicalparameter of the subject from the response signal detected from the eyeof the subject when the eye of the subject is in alignment with respectto the at least one of the interrogation signal source and the responsesignal sensor. In addition to the foregoing, other method aspects aredescribed in the claims, drawings, and text forming a part of thedisclosure set forth herein.

In one aspect, an article of manufacture includes, but is not limitedto, one or more non-transitory machine-readable data storage mediabearing one or more instructions for: delivering an interrogation signalto an eye of the subject with an interrogation signal source; detectinga response signal from the eye of the subject with a response signalsensor; determining whether the eye of the subject is in alignment withrespect to at least one of the interrogation signal source and theresponse signal sensor; and determining a physiological parameter of thesubject from the response signal detected from the eye of the subjectwhen the eye of the subject is in alignment with respect to the at leastone of the interrogation signal source and the response signal sensor.In addition to the foregoing, other aspects of articles of manufactureincluding one or more non-transitory machine-readable data storage mediabearing one or more instructions are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system for sensing information from an eye of a subjectincludes, but is not limited to: an interrogation signal source fordelivering an interrogation signal to an eye of a subject; a responsesignal sensor for sensing a response signal produced by the eye of thesubject responsive to the interrogation signal; a gaze signal sensoradapted for receiving a gaze signal containing information indicative ofa gaze direction of an eye of the subject; at least one actuatorconfigured to adjust at least one of the interrogation signal source andthe response signal sensor to bring at least one of the interrogationsignal source and the response signal sensor into alignment with the eyeof the subject; and signal processing circuitry including: a responsesignal processor configured to process a response signal sensed from theeye of the subject to determine a physiological parameter from theresponse signal; a gaze signal processor configured to determine thegaze direction of the eye of the subject based upon the gaze signal; analignment detector configured to determine whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the gaze direction; and an actuator controllerconfigured to: determine a target position for at least one of theinterrogation signal source and the response signal sensor based atleast in part on the gaze direction; and generate an actuator controlsignal to drive the at least one actuator to adjust at least one of theinterrogation signal source and the response signal sensor to bring atleast one of the interrogation signal source and the response signalsensor into alignment with the eye of the subject. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system for controlling the sensing of information froman eye of a subject includes, but is not limited to: signal processingcircuitry including: a gaze signal input adapted to receive a gazesignal containing information indicative of a gaze direction of the eyeof the subject sensed from at least an eye of the subject; a responsesignal input adapted to receive a response signal sensed from the eye ofthe subject by a response signal sensor responsive to delivery of aninterrogation signal to the eye of the subject; a response signalprocessor configured to process a response signal sensed from the eye ofthe subject to determine a physiological parameter from the responsesignal; a gaze signal processor configured to determine the gazedirection of the eye of the subject based upon the gaze signal; analignment detector configured to determine whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the gaze direction; and an actuator controllerconfigured to: determine a target position for at least one of theinterrogation signal source and the response signal sensor based atleast in part on the gaze direction; and generate an actuator controlsignal to drive the at least one actuator to adjust at least one of theinterrogation signal source and the response signal sensor to bring atleast one of the interrogation signal source and the response signalsensor into alignment with the eye of the subject. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system includes, but is not limited to a housing; aninterrogation signal source housed in the housing and adapted fordelivering an interrogation signal to an eye of a subject, theinterrogation signal source including at least one light source and atleast one optical system; a response signal sensor housed within thehousing and adapted for sensing a response signal produced by the eye ofthe subject responsive to the interrogation signal, the response signalcontaining information regarding a physiological parameter of thesubject; an input structure adapted for receiving an input signal; atleast one actuator configured to adjust at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the input signal to bring at least one of theinterrogation signal source and the response signal sensor intoalignment with the eye of the subject; an output structure adapted fortransmitting an output signal; and mounting means adapted for mountingthe housing with respect to a display in such a manner that theinterrogation signal source and response signal sensor are alignablewith the eye of the subject during normal use of the display by thesubject. In addition to the foregoing, other system aspects aredescribed in the claims, drawings, and text forming a part of thedisclosure set forth herein.

In one aspect, a method of measuring information from an eye of asubject includes, but is not limited to delivering an interrogationsignal to the eye of the subject with an interrogation signal source;detecting a response signal from the eye of the subject with a responsesignal sensor; receiving a signal indicative of the gaze direction ofthe eye of the subject from a gaze signal sensor; determining whetherthe eye of the subject is in alignment with respect to at least one ofthe interrogation signal source and the response signal sensor; if theeye of the subject is not in alignment with respect to the at least oneof the interrogation signal source and the response signal sensor,actuating at least one actuator configured to adjust at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the signal from the gaze signal sensor to bring atleast one of the interrogation signal source and the response signalsensor into alignment with the eye of the subject; determining aphysiological parameter of the subject from the response signal detectedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor; and causing a signal indicative of thephysiological parameter to be transmitted to an external device. Inaddition to the foregoing, other method aspects are described in theclaims, drawings, and text forming a part of the disclosure set forthherein.

In one aspect, an article of manufacture includes, but is not limitedto, one or more non-transitory machine-readable data storage mediabearing one or more instructions for: delivering an interrogation signalto the eye of the subject with an interrogation signal source; detectinga response signal from the eye of the subject with a response signalsensor; receiving a signal indicative of the gaze direction of the eyeof the subject from a gaze signal sensor; determining whether the eye ofthe subject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor; if the eyeof the subject is not in alignment with respect to the at least one ofthe interrogation signal source and the response signal sensor,actuating at least one actuator configured to adjust at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the signal from the gaze signal sensor to bring atleast one of the interrogation signal source and the response signalsensor into alignment with the eye of the subject; determining aphysiological parameter of the subject from the response signal detectedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor; and causing a signal indicative of thephysiological parameter to be transmitted to an external device. Inaddition to the foregoing, other aspects of articles of manufactureincluding one or more non-transitory machine-readable data storage mediabearing one or more instructions are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system for sensing information from an eye of a subjectincludes, but is not limited to: an interrogation signal source fordelivering an interrogation signal to an eye of a subject; a responsesignal sensor for sensing a response signal produced by the eye of thesubject responsive to the interrogation signal; and signal processingcircuitry including: a response signal processor configured to process aresponse signal sensed from the eye of the subject to determine aphysiological parameter from the response signal; and a schedulingcontroller configured to direct collection of samples of thephysiological parameter according to a schedule. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system for controlling the sensing of information froman eye of a subject includes, but is not limited to: signal processingcircuitry including: a response signal input adapted to receive aresponse signal sensed from the eye of the subject by a response signalsensor responsive to delivery of an interrogation signal to the eye ofthe subject; and a response signal processor configured to process theresponse signal sensed from the eye of the subject by the responsesignal sensor to determine a physiological parameter from the responsesignal; and a scheduling controller configured to direct collection ofsamples of the physiological parameter according to a schedule. Inaddition to the foregoing, other system aspects are described in theclaims, drawings, and text forming a part of the disclosure set forthherein.

In one aspect, a system includes, but is not limited to a housing; aninterrogation signal source housed in the housing and adapted fordelivering an interrogation signal to an eye of a subject, theinterrogation signal source including at least one light source and atleast one optical system; a response signal sensor housed within thehousing and adapted for sensing a response signal produced by the eye ofthe subject responsive to the interrogation signal, the response signalcontaining information regarding a physiological parameter of thesubject; signal processing circuitry including: a response signalprocessor configured to process a response signal sensed from the eye ofthe subject to determine a physiological parameter from the responsesignal; and a scheduling controller configured to direct collection ofsamples of the physiological parameter according to a schedule; anoutput structure adapted for transmitting an output signal; and mountingmeans adapted for mounting the housing with respect to a display in sucha manner that the interrogation signal source and response signal sensorare alignable with the eye of the subject during normal use of thedisplay by the subject. In addition to the foregoing, other systemaspects are described in the claims, drawings, and text forming a partof the disclosure set forth herein.

In one aspect, a method of measuring information from an eye of asubject includes, but is not limited to; delivering an interrogationsignal to the eye of the subject with an interrogation signal source;detecting a response signal from the eye of the subject with a responsesignal sensor; processing a response signal sensed from the eye of thesubject to determine a physiological parameter from the response signal;determining whether the eye of the subject is in alignment with respectto at least one of the interrogation signal source and the responsesignal sensor; determining a physiological parameter of the subject fromthe response signal detected from the eye of the subject when the eye ofthe subject is in alignment with respect to the at least one of theinterrogation signal source and the response signal sensor; andcollecting samples of the physiological parameter according to aschedule under the direction of a scheduling controller. In addition tothe foregoing, other method aspects are described in the claims,drawings, and text forming a part of the disclosure set forth herein.

In one aspect, an article of manufacture includes, but is not limitedto, one or more non-transitory machine-readable data storage mediabearing one or more instructions for: delivering an interrogation signalto the eye of the subject with an interrogation signal source; detectinga response signal from the eye of the subject with a response signalsensor; processing a response signal sensed from the eye of the subjectto determine a physiological parameter from the response signal;determining whether the eye of the subject is in alignment with respectto at least one of the interrogation signal source and the responsesignal sensor; determining a physiological parameter of the subject fromthe response signal detected from the eye of the subject when the eye ofthe subject is in alignment with respect to the at least one of theinterrogation signal source and the response signal sensor; andcollecting samples of the physiological parameter according to aschedule under the direction of a scheduling controller. In addition tothe foregoing, other aspects of articles of manufacture including one ormore non-transitory machine-readable data storage media bearing one ormore instructions are described in the claims, drawings, and textforming a part of the disclosure set forth herein.

In one aspect, a system for sensing information from an eye of a subjectincludes, but is not limited to: an interrogation signal source fordelivering an interrogation signal to an eye of a subject; a responsesignal sensor for sensing a response signal produced by the eye of thesubject responsive to the interrogation signal; a gaze attractor adaptedto attract the gaze of the subject to thereby cause the eye of thesubject to move into alignment with at least one of the interrogationsignal source and the response signal sensor; and signal processingcircuitry including: a response signal processor configured to process aresponse signal sensed from the eye of the subject when the eye of thesubject is in alignment with respect to the at least one of theinterrogation signal source and the response signal sensor to determinea physiological parameter from the response signal. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system for controlling the sensing of information froman eye of a subject includes, but is not limited to: signal processingcircuitry including: a gaze attractor controller adapted to drive a gazeattractor to cause the eye of the subject to move into alignment with atleast one of the interrogation signal source and the response signalsensor; a response signal input adapted to receive a response signalsensed from the eye of the subject by a response signal sensorresponsive to delivery of an interrogation signal to the eye of thesubject; and a response signal processor configured to process aresponse signal sensed from the eye of the subject when the eye of thesubject is in alignment with respect to the at least one of theinterrogation signal source and the response signal sensor to determinea physiological parameter from the response signal. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the disclosure set forth herein.

In one aspect, a system includes, but is not limited to a housing; aninterrogation signal source housed in the housing and adapted fordelivering an interrogation signal to an eye of a subject, theinterrogation signal source including at least one light source and atleast one optical system; a response signal sensor housed within thehousing and adapted for sensing a response signal produced by the eye ofthe subject responsive to the interrogation signal, the response signalcontaining information regarding a physiological parameter of thesubject; a gaze attractor adapted to attract the gaze of the subject tothereby cause the eye of the subject to move into alignment with atleast one of the interrogation signal source and the response signalsensor; an output structure adapted for transmitting an output signal;mounting means adapted for mounting the housing with respect to adisplay in such a manner that the interrogation signal source andresponse signal sensor are alignable with the eye of the subject duringnormal use of the display by the subject. In addition to the foregoing,other system aspects are described in the claims, drawings, and textforming a part of the disclosure set forth herein.

In one aspect, a method of measuring information from an eye of asubject includes, but is not limited to; delivering an interrogationsignal to the eye of the subject with an interrogation signal source;detecting a response signal from the eye of the subject with a responsesignal sensor; controlling a gaze attractor to cause the eye of thesubject to move into alignment with at least one of the interrogationsignal source and the response signal sensor; and determining aphysiological parameter of the subject from the response signal detectedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor. In addition to the foregoing, other methodaspects are described in the claims, drawings, and text forming a partof the disclosure set forth herein.

In one aspect, an article of manufacture includes, but is not limitedto, one or more non-transitory machine-readable data storage mediabearing one or more instructions for: delivering an interrogation signalto the eye of the subject with an interrogation signal source; detectinga response signal from the eye of the subject with a response signalsensor; controlling a gaze attractor to cause the eye of the subject tomove into alignment with at least one of the interrogation signal sourceand the response signal sensor; and determining a physiologicalparameter of the subject from the response signal detected from the eyeof the subject when the eye of the subject is in alignment with respectto the at least one of the interrogation signal source and the responsesignal sensor. In addition to the foregoing, other aspects of articlesof manufacture including one or more non-transitory machine-readabledata storage media bearing one or more instructions are described in theclaims, drawings, and text forming a part of the disclosure set forthherein.

In addition to the foregoing, various other method and/or system and/orarticles of manufacture including one or more non-transitorymachine-readable data storage media bearing one or more instructions areset forth and described in the teachings such as text (e.g., claimsand/or detailed description) and/or drawings of the present disclosure.

The foregoing is a summary and thus may contain simplifications,generalizations, inclusions, and/or omissions of detail; consequently,those skilled in the art will appreciate that the summary isillustrative only and is NOT intended to be in any way limiting. Otheraspects, features, and advantages of the devices and/or processes and/orother subject matter described herein will become apparent by referenceto the detailed description, the corresponding drawings, and/or in theteachings set forth herein.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

For a more complete understanding of embodiments, reference now is madeto the following descriptions taken in connection with the accompanyingdrawings. The use of the same symbols in different drawings typicallyindicates similar or identical items, unless context dictates otherwise.The illustrative embodiments described in the detailed description,drawings, and claims are not meant to be limiting. Other embodiments maybe utilized, and other changes may be made, without departing from thespirit or scope of the subject matter presented here.

FIG. 1 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 2 is an illustration of the anatomy of an eye.

FIG. 3 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 4 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 5A depicts an example of an interrogation signal source andresponse signal sensor combination for detecting various physiologicalparameters.

FIG. 5B depicts an example of an interrogation signal source andresponse signal sensor combination for detecting various physiologicalparameters.

FIG. 5C depicts an example of an interrogation signal source andresponse signal sensor combination for detecting various physiologicalparameters.

FIG. 5D depicts an example of an interrogation signal source andresponse signal sensor combination for detecting a physiologicalparameter.

FIG. 5E depicts example of an interrogation signal source and responsesignal sensor combination for detecting a physiological parameter.

FIG. 6 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 7 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 8 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 9 is an illustration of an example a system used for monitoringhealth parameters of a computer user.

FIG. 10 is a block diagram of a system for controlling the sensing ofinformation from an eye of a subject.

FIG. 11 is a block diagram of a system for controlling the sensing ofinformation from an eye of a subject.

FIG. 12 is a block diagram of a system for controlling the sensing ofinformation from an eye of a subject.

FIG. 13 illustrates several embodiments of a system for sensinginformation from an eye of a subject.

FIG. 14 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 15 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 16 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 17 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 18 illustrates an embodiment of a system including a stimulationunit.

FIG. 19 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 20 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 21 illustrates an article of manufacture including non-transitorymachine-readable data storage media bearing instructions for performinga method of measuring information from an eye of a subject.

FIG. 22 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 23 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 24 illustrates an embodiment of a system for sensing informationfrom an eye of a subject at an airline ticket kiosk.

FIG. 25 is a block diagram of a system for controlling the sensing ofinformation from an eye of a subject.

FIG. 26 is a block diagram of a system for sensing of information froman eye of a subject.

FIG. 27 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 28 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 29 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 30 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 31 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 32 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 33 illustrates an article of manufacture including non-transitorymachine-readable data storage media bearing instructions for performinga method of measuring information from an eye of a subject.

FIG. 34 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 35 is a block diagram of an embodiment of a system for controllingthe sensing of information from an eye of a subject.

FIG. 36 is a block diagram of a system for sensing information from aneye of a subject.

FIG. 37 illustrates an embodiment of a system for sensing informationfrom a hospital patient according to a schedule.

FIG. 38 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 39 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 40 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 41 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 42 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 43 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 44 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 45 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 46 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 47 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 48 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 49 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 50 illustrates an article of manufacture including non-transitorymachine-readable data storage media bearing instructions for performinga method of measuring information from an eye of a subject.

FIG. 51 illustrates an embodiment of a system for sensing informationfrom an eye of a subject.

FIG. 52 is a block diagram of a system for controlling the sensing ofinformation from an eye of a subject.

FIG. 53 is a block diagram of an embodiment of a system for sensinginformation from an eye of a subject.

FIG. 54 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 55 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 56 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 57 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 58 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 59 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 60 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 61 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 62 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 63 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 64 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 65 is a flow diagram of a method of measuring information from aneye of a subject.

FIG. 66 illustrates an article of manufacture including non-transitorymachine-readable data storage media bearing instructions for performinga method of measuring information from an eye of a subject.

FIG. 67 is a generalized block diagram of an embodiment of a system.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

FIG. 1 depicts a system 100 for sensing information from an eye 102 of asubject 104, which includes a gaze signal sensor 106 adapted forreceiving a gaze signal 108 containing information indicative of a gazedirection of eye 102 of subject 104; an interrogation signal source 110for delivering an interrogation signal 112 to eye 102 of subject 104; aresponse signal sensor 114 for sensing response signal 116 produced bythe eye 102 responsive to interrogation signal 112; signal processingcircuitry 118 including a gaze signal processor 120 configured todetermine the gaze direction of eye 102 based upon gaze signal 108;alignment detector 122 configured to determine whether eye 102 ofsubject 104 is in alignment with respect to at least one of theinterrogation signal source 110 or response signal sensor 114 based atleast in part upon the gaze direction; and response signal processor 124configured to process response signal 116 sensed from eye 102 of subject104 by the response signal sensor 114 when eye 102 is in alignment withrespect to the at least one of the interrogation signal source 110 orresponse signal sensor 114 to determine a physiological parameter 126from response signal 116.

Interrogation signal source 110 includes light source 130, opticalsystem 132, and actuator 134 for adjusting light source 130 and/oroptical system 132 to control the position and focal distance ofinterrogation signal 112. Response signal sensor 114 includes lightsensor 136, optical system 138, and actuator 140 for manipulating thelight sensor 136 and/or optical system 138. Optical systems 132 and 138(and other optical systems described herein) may include variouscomponents for controlling different aspects of the optical signals,(e.g. focus, direction, collimation, light polarization, wavelengthcomposition) including, for examples, lenses, mirrors, reflectors,filters, diffraction gratings, etc. as are well known to those havingskill in the optical arts. Response signal sensor 114 may be adapted tosense response signal 116 from an interior of the eye 102 of subject 104responsive to the interrogation signal. For example, response signalgenerally may be focused to detect a response signal reflect from aparticular structure in the interior eye 102, and or be adapted to sensefrequency components found in signals reflected from a region/structureof interest within eye 102.

FIG. 2 depicts an eye 200 showing various internal structures from whicha response signal can be detected responsive to an interrogation signal,including lens 202, aqueous humor 204, vitreous humor 206, or retina208. Also depicted are iris 210 and optic nerve 212. As two specificexamples, FIG. 2 depicts interrogation signal 220 that is reflected offa front surface of lens 202 to form response signal 222, andinterrogation signal 224 that is reflected off retina 208 to formresponse signal 226.

Referring back to FIG. 1, gaze signal sensor 106 may include varioustypes of sensing devices, including, e.g. an infrared camera 142 or aCCD camera 144. Gaze signal sensor 106 and response signal sensor 114may be different sensors, as depicted in FIG. 1, or the same sensor asdepicted in FIG. 3. If different sensors, they may be different sensorsof the same type, or different sensors of different types. FIG. 3depicts a system 300 in which a single signal source is used as acombined gaze tracking stimulus source interrogation signal source 320,which includes light source 330, optical system 332 and actuator 334,and a single sensor is used as gaze signal sensor/response signal sensor302, which includes light sensor 306, optical system 308 and actuator310. Gaze signal/response signal 304 is produced by eye 102 in responseto gaze tracking stimulus/interrogation signal 312. The sensed responsesignal is directed to gaze signal processor 120 and response signalprocessor 124, which along with alignment detector 122, components ofsignal processing circuitry 118.

As shown in FIG. 1, system 100 for sensing information from eye 102 ofsubject 104 may also include at least one gaze tracking stimulus source150 adapted to deliver gaze tracking stimulus 152 to at least eye 102 ofsubject 104, wherein the gaze signal 108 is produced in response to gazetracking stimulus 152. Here and elsewhere, elements of a figureindicated with a dashed line are not required in all embodiments. Gazetracking stimulus source 150 may include, for example, an infra-redsource 154 or a near infra-red source 156. A gaze signal sensor 106 thatincludes an infra-red sensor (e.g., an infrared camera 142) may be usedin combination with an infra-red source 154, and a gaze signal sensorthat includes a near infra-red sensor (for example, a near infra-redcamera 146) may be used in combination with a near infra-red source 156.Gaze tracking stimulus source 150 may include one or a plurality oflight sources. Gaze signal sensor 106 may include one or a plurality ofoptical sensors, an optical sensor array, and/or a camera (142, 144,146, or 148).

Eye tracking to determining gaze direction is performed by analysis ofgaze signal 108 sensed by gaze signal sensor 106 with gaze signalprocessor 120. As depicted in FIG. 1, gaze signal sensor can include acamera, which can be a smart camera that can capture images of a user'seyes, process them and issue control commands within a millisecond timeframe. Image data may include results of visual spectrum imaging,infrared imaging, ultrasound imaging. Smart cameras are commerciallyavailable (e.g., Hamamatsu's Intelligent Vision System;http://jp.hamamatsu.com/en/product_info/index.html). Such image capturesystems may include dedicated processing elements for each pixel imagesensor. Other camera systems for use as gaze signal sensors may include,for example, a pair of infrared charge coupled device cameras tocontinuously monitor pupil size and position. This can be done as theeye follows a moving visual target, and can provide real-time datarelating to pupil accommodation relative to objects on a display (e.g.,http://jp.hamamatsu.com/en/rd/publication/scientific_american/common/pdf/scientific_(—)0608.pdf).FIG. 1 depicts gaze signal processor 120 as separate from gaze signalsensor 106; however, in some embodiments, some or all of the gaze signalprocessor 120 may be packaged with and/or formed integrally with thegaze signal sensor 106.

Eye movement and/or pupil movement may also be measured by video-basedeye trackers. In these systems, a camera (the gaze signal sensor 106)focuses on one or both eyes and records eye movement as the viewer looksat a stimulus. Contrast may be used to locate the center of the pupil,and infrared and near-infrared non-collimated light (the gaze trackingstimulus source 150) may be used to create a corneal reflection. Thevector between these two features can be used to compute gazeintersection with a surface after a calibration for a subject.

Two types of eye tracking techniques include bright pupil eye trackingand dark pupil eye tracking. Their difference is based on the locationof the illumination source (gaze tracking stimulus source) with respectto the optical system. If the illumination is coaxial with the opticalpath, then the eye acts as a retroreflector as the light reflects offthe retina, creating a bright pupil effect similar to red eye. If theillumination source is offset from the optical path, then the pupilappears dark. Thus, in some embodiments, the gaze tracking stimulussource and the gaze response signal sensor are co-aligned.Alternatively, the gaze tracking stimulus source and the gaze responsesignal sensor be separately aligned and located.

Bright Pupil tracking creates greater iris/pupil contrast allowing formore robust eye tracking that is less dependent upon iris pigmentationand greatly reduces interference caused by eyelashes and other obscuringfeatures. It also allows for tracking in lighting conditions rangingfrom total darkness to very bright light. However, bright pupiltechniques are not recommended for tracking outdoors as extraneousinfrared (IR) sources may interfere with monitoring.

Most eye tracking systems use a sampling rate of at least 30 Hz.Although 50/60 Hz is most common, many video-based eye trackers run at240, 350 or even 1000/1250 Hz, which is recommended in order to capturethe detail of the very rapid eye movements during reading, for example.

Eye movements are typically divided into fixations, when the eye gazepauses in a certain position, and saccades, when the eye gaze moves toanother position. A series of fixations and saccades is called ascanpath. Most information from the eye is made available during afixation, not during a saccade. The central one or two degrees of thevisual angle (the fovea) provide the bulk of visual information; inputfrom larger eccentricities (the periphery) generally is lessinformative. Therefore the locations of fixations along a scanpathindicate what information loci on the stimulus were processed during aneye tracking session. On average, fixations last for around 200milliseconds during the reading of linguistic text, and 350 millisecondsduring the viewing of a scene. Preparing a saccade towards a new goaltakes around 200 milliseconds. Scanpaths are useful for analyzingcognitive intent, interest, and salience. Other biological factors (someas simple as gender) may affect the scanpath as well. Eye tracking inhuman-computer interaction typically investigates the scanpath forusability purposes, or as a method of input in gaze-contingent displays,also known as gaze-based interfaces.

Commercial eye tracking software packages can analyze eye tracking andshow the relative probability of eye fixation at particular locations.This allows for a broad analysis of which locations received attentionand which ones were ignored. Other behaviors such as blinks, saccades,and cognitive engagement can be reported by commercial softwarepackages.

Signal processing circuitry 118 includes alignment detector 122. As usedherein, the interrogation signal source being “in alignment” withrespect to the eye of the subject refers to positioning of the eye ofthe subject with respect to the interrogation signal source such that,for example, an interrogation signal 112 from the interrogation signalsource 110 is able to enter and/or interact with the eye 102 of thesubject so that a measurement can be obtained from the eye of thesubject. Alignment of eye 102 of subject 104 with respect to responsesignal sensor 114 refers to positioning of eye 102 of subject 104 withrespect to the response signal sensor 114 such that response signal 116from eye 102 of subject 104 can reach and can be sensed by the responsesignal sensor 114. Determining alignment of the eye of the subject withrespect to the interrogation signal source 110 and the response signalsensor 114 may include determining the gaze direction of the eye of thesubject, and comparing the gaze direction of the eye with informationregarding the position and orientation of the interrogation signalsource and/or response signal sensor. Alternatively, or in addition,alignment of the eye of the subject with respect to the interrogationsignal source and the response signal sensor can be detected through thequality of the signal, e.g., by higher signal strength in wavelengths ofinterest. Such determining or detection of alignment is carried out byalignment detector 122. It will be appreciated that the eye may beconsidered “in alignment” with the response signal sensor 114 orinterrogation signal source 110 when the response signal sensor orinterrogation signal source lies within a specified number of degrees ofthe gaze direction, and may not necessarily be located exactly in linewith the gaze direction. In particular, if the interrogation signalsource has a broad output angle, or the response signal sensor has abroad input angle, then components may be considered to be “inalignment,” in that a measurement may be obtained, even if thecomponents are not exactly in line. In some embodiments, the system maybe configured to deliver the interrogation signal to the eye of thesubject with the interrogation signal source only when the eye of thesubject is in alignment with the interrogation signal source and theresponse signal sensor.

Interrogation signal source 110 and response signal sensor 114 areselected such that a signal produced by the eye in response to theinterrogation signal 112 is detectable by response signal sensor 114.For example, as depicted in FIG. 1, the interrogation signal source isan optical signal source, and an optical response signal is produced inresponse thereto, which is detectable by an optical response signalsensor. Optical signal sources may be characterized in terms ofwavelength/waveband of light emitted (which may be visible, infrared,near-infrared, or mid-infrared, for example). Wavelength, phase,amplitude and polarization of light emitted by an optical interrogationsignal source may be modified, e.g. through the use of filters ordiffraction gratings. An optical response signal sensor used incombination with an optical interrogation signal source may beconfigured (e.g. through the use of suitable filters or diffractiongratings) to sense an optical signal having particular properties, e.g.,wavelength or polarization, which may be the same or different that thewavelength or polarization of the light produced by the interrogationsignal source. In one aspect, the interrogation signal source is adaptedto produce light having a first polarization, wherein the responsesignal sensor is adapted to detect light having a second polarization.The first polarization and the second polarization may be the same ordifferent.

In some embodiments described herein, a system may include other typesof interrogation signal source and response signal sensor. For example,as shown in FIG. 4, an acoustic (ultrasonic) interrogation signal source402 a and acoustic (ultrasonic) response signal sensor 406 a are used.An ultrasonic interrogation signal 404 a can be used to measure asubject's hear rate, for example, as will be described in greater detailherein below. In some embodiments, more than one interrogation signalsource and response signal sensor may be used. FIG. 4 depicts opticalinterrogation signal sources 402 b and 402 c which generate opticalinterrogation signals 404 b and 404 c, respectively, in addition toultrasonic interrogation signal source 402 a, and optical signal sensors406 b and 406 c in addition to ultrasonic response signal sensor 406 a.Use of multiple different interrogation signal sources and sensorspermits detection of multiple different physiological parameters 426 a,426 b, and 426 c. Gaze signal sensor 106, gas tracking stimulus source150, gaze signal processor and alignment detector 122 are as describedin connection with FIG. 1. Response signal processor 424 is configuredto process response signals 408 a, 408 b, and 408 c to determinephysiological parameters 426 a, 426 b, and 426 c. In some aspects,multiple sensors may be used to detect multiple different physiologicalparameters. However, in some embodiments it may be desirable to usemultiple sensors in the detection of a single parameter.

Different source/sensor combinations can be used to detect differentphysiological parameters. Examples of combinations of interrogationsignal source and response signal sensor and sensed parameters aredepicted in FIGS. 5A-5E. For example, as shown in FIG. 5A, thecombination of interrogation signal source that includes a broadspectrum light source 502 a and response signal sensor that includes aspectrometer 506 a based on a CCD array may be suited for detecting avariety of analytes, e.g. sodium salts 526 a 1, glucose 526 a 2,proteins 526 a 3, or lipids 526 a 4 from the aqueous humor 504 a of theeye 102, as well as other analytes, for example as described U.S. PatentAppl. No. 2011/0184262 by Menon published on Jul. 28, 2011, which isincorporated herein by reference.

As shown in FIG. 5B, the combination of an interrogation signal sourcethat includes a near-infrared light source 502 b and response signalsensor that includes near-infrared camera 506 b may be suited fordetecting biometric identification 526 b 1 from retina 504 b 1 orbiometric identification 526 b 2 from iris 504 b 2, for example asdescribed in U.S. Pat. No. 5,572,596 issued to Wildes et al. on Nov. 5,1996 and U.S. Pat. No. 4,641,349 issued to Flom et al. on Feb. 3, 1987,each of which is incorporated herein by reference.

As shown in FIG. 5C, the combination of interrogation signal source thatincludes a tunable laser source 502 c and response signal sensor thatincludes a Raman spectroscope 506 c based on a CCD camera may be suitedfor detecting, e.g. hormones 526 c such as epinephrine 526 c 1,norepinephrine 526 c 2, or hydrocortisone 526 c 3, in aqueous humor 504c 1, or blood vessels 504 c 2 in conjunctiva or retina, for example asdescribed U.S. Pat. No. 6,961,599 issued to Lambert et al. on Nov. 1,2005, which is incorporated herein by reference.

As shown in FIG. 5D, the combination of interrogation signal source thatincludes a mid-infrared light source 502 d and response signal sensorthat includes a mid-infrared detector 506 d may be suited for detecting,e.g. glucose 526 d in blood vessels 504 d in sclera, for example asdescribed in U.S. Pat. No. 6,958,039 issued to Burd et al. on Oct. 25,2005, which is incorporated herein by reference.

As shown in FIG. 5E, The combination of interrogation signal source thatincludes tunable laser 502 e and response signal sensor that includesbroad spectrum pyroelectric detector 506 e may be suited for detecting,e.g. warfarin 526 e in blood vessels in the sclera 504 e, (see e.g., theData Sheet: “Warfarin IR Spectrum” which is incorporated herein byreference).

The detection methods summarized in FIGS. 5A-5E are described in greaterdetail in connection with various examples of embodiments describedherein. The response signal may be indicative of, e.g., a feature of thevasculature of the eye of the subject, or a biometric identification ofthe subject. A response signal detected by a camera may be an image,such as an image of the vasculature of the retina, which may be used ina biometric identification. Other characteristics of the vasculature ofthe eye (e.g. movement of the vasculature of the eye) may be indicativeof other physiological parameters, which may be derived therefrom.

In various embodiment described herein, the physiological parameter maybe a measurement of and/or indicative of heart rate or pulse rate, bloodflow, a temperature (e.g. body temperature), or a substance (e.g., achemical component) in the eye of the subject, which may be, forexample, a substance in the aqueous humor or vitreous humor, or in theblood of the retina, conjunctiva, or sclera. A wide variety ofsubstances in blood, aqueous humor or vitreous humor can be detectedusing spectroscopic methods, as described herein and as known to thoseof skill in the relevant art. Substances that may be detected include,but are not limited to, glucose, oxygen, glycosylated hemoglobin, salts,proteins, lipids, gases, hormones, and drugs. The physiologicalparameter may be measured directly, or derived from a parameter that ismeasured directly. Blood flow may be determined, for example, with laserDoppler or thermal flowmetry based on optical temperature measurements.Heart rate or pulse rate can be determined from ocular pulsemeasurements (see e.g., U.S. Pat. No. 3,948,248 issued to Zuckerman etal. on Apr. 6, 1976 which is incorporated herein by reference). Otherphysiological parameters may be measured by methods known to thosehaving skill in the art.

Multiple physiological parameters can be determined from a subjectthrough the use of multiple interrogation signal sources and sensors, orby using different processing signal approaches on data obtained withthe same interrogation signal source(s)/response signal.

As shown in FIG. 6, in an embodiment, interrogation signal source 602may be adapted to deliver a pulsed interrogation signal 604. At leastone of response signal sensor 606 and signal processing circuitry 618 isconfigured to gate detection of the response signal 608 relative to thepulsed interrogation signal 604. In an aspect, signal processingcircuitry 618 is configured to combine multiple response signalsproduced by the eye of the subject in response to multiple pulses of thepulsed interrogation signal. Signal processing circuitry 618 may combinethe multiple response signals by various methods, e.g., by summingand/or averaging the multiple response signals, as indicated at 620 and622, respectively, or by determining a moving average or weighted sum ofthe multiple response signals, as indicated at 624 and 626,respectively. Combining response signals may be beneficial in order toproduce physiological parameter data 426 that has an improvedsignal-to-noise ratio or that more accurately represents thephysiological parameter being measured. As used herein, the term“signal” refers to a signal of interest within the relevant context, andthe term “noise” refers to any signal that is not of interest within therelevant context.

As shown in FIG. 7, an interrogation signal source 702 c may be adaptedto deliver an interrogation signal containing multiple wavelengths oflight λ₁, λ₂, λ₃ (for example, interrogation signal source may be abroad spectrum source). The system may include a first response signalsensor 706 a configured to sense a first response signal 708 a producedby the eye of the subject responsive to a first wavelength component(λ₁) of the interrogation signal 704 c, and a second response signalsensor 706 b configured to sense a second response signal 708 b producedby the eye of the subject responsive to a second wavelength component(λ₂) of the interrogation signal 704 c. Alternatively, a single sensormay sense response signals produced at two or more differentwavelengths.

Alternatively, the system may include at least a first interrogationsignal source 702 a configured to deliver a first interrogation signal704 a having a first optical wavelength (λ₁) and at least a secondinterrogation signal source 702 b configured to deliver a secondinterrogation signal 704 b having a second optical wavelength (λ₂).Response signals 708 a and 708 b are produced in response to firstinterrogation signal 704 a and second interrogation signal 704 b, anddetected by response signal sensors 706 a and 706 b respectively. Signalprocessing circuitry 718 including response signal processor 724 may beconfigured to process a first response signal 708 a sensed from eye 102of subject 104 in response to the first interrogation signal 704 a and asecond response signal 708 b sensed from eye 102 of subject 104 inresponse to second interrogation signal 704 b by comparing the first andsecond response signals with comparator 730 to determine thephysiological parameter 732. System 700 may be configured to deliver thefirst interrogation signal 704 a simultaneously with respect to thesecond interrogation signal 704 b, or sequentially with respect to thesecond interrogation signal 704 b.

In an embodiment, the interrogation signal source and the responsesignal sensor are co-aligned. Alternatively, the interrogation signalsource and the response signal sensor may be separately aligned andlocated. If the interrogation signal source and response signal sensorare co-aligned, it may be necessary to only detect the alignment of theeye of the subject with one of the interrogation signal source andresponse signal sensor, in that alignment with one is indicative ofalignment with the other. If, on the other hand, interrogation signalsource and response signal sensor are separately located and aligned, itmay be necessary to detect the alignment of the eye with regard to each.This is particularly the case if the output angle of the interrogationsignal source and the input angle of the response signal sensor arenarrowly focused and tight alignment is required in order to obtain agood measurement. If one of the interrogation signal source and responsesignal sensor is relatively unfocused and/or untargeted (having a wideinput/output angle) and one has a narrow/focused input/output angle, itsalignment with the eye may not be critical and detection of suchalignment may not be required. In addition, if a detector but no sourceis used (e.g., in the case that a detectable response signal can beobtained in ambient light), again, it would only be necessary to detectalignment of the eye of the subject with respect to the response signalsensor.

As depicted in FIG. 8, a system 800 for sensing information from eye 102of subject 104 may also include an output structure 810 adapted tooutput a signal relating to the determined physiological parameter 126.For example, output structure 810 can include data transmissionstructure 812, a data storage structure 814, a display 816, an audiooutput 818, or a visual output 820. As an example, the system mayinclude a display adapted to display information relating to thedetermined physiological parameter. The display may be a video monitor(including but not limited to a television display), a computer display(including but not limited to a display on a desktop, laptop, tabletcomputer, personal digital assistance, or any other stationary, portableor handheld computing devices), a video game display, a telephonedisplay (including, but not limited to, a display on a smart phone), ora terminal of a data processing device (any type of device having dataprocessing capability). The display may be incorporated in a wearableitem (e.g. eyewear, headware, jewelry, an article of clothing, a badge,a bandage, an adhesive patch, a wristwatch, a cuff, a sleeve, awristband, an armband, a helmet, a physiological support such as a castor brace, or a wearable a positioning structure configured to surround aportion of the subject), an article of furniture, an article of medicalor health-care related equipment (e.g., for use in a hospital, clinic,physician's office, care facility, or home), an article of exerciseequipment (e.g., a treadmill, exercise bicycle, elliptical trainer), ora vehicle (e.g. as a display in a dashboard, control panel, or drop-downor seat-back display of an automobile, a truck, a train, an airplane, amotorcycle, or a boat). The particular choice of display may depend uponthe intended application of the system, e.g. whether it is to be usedfor a medical or health-related application or business or securityapplication, or for individual or institutional use, as illustrated bythe examples provided herein. System 800 may include multiple outputstructures to permit data or information to be output in more than oneformat or for more than one purpose.

EXAMPLE 1 An Unobtrusive Eye Interrogation System Attached to a ComputerMonitor to Measure Health Parameters of a Computer User

FIG. 9 illustrates an example of a system as described generally inconnection with FIG. 1. FIG. 9 illustrates an eye interrogation system900 positioned relative to computer monitor 902. Eye interrogationsystem 900 detects gaze alignment and interrogates the eye 904 of asubject (computer user) 906 to determine health parameters while subject906 works at the computer 908. To detect gaze alignment, a gaze trackingsystem is used to detect when the subject 906 looks at the interrogationsource and/or the interrogation sensor. The gaze tracking systemincludes gaze tracking stimulus source which includes IR light source910 and gaze signal sensor which includes IR camera 912, which detectsthe reflection of IR light from the eyes 904 of the subject 906. Forexample, a gaze tracking system for monitoring eye position is availablefrom Seeing Machines Inc., Tucson, Ariz. (see e.g., the SpecificationSheet: “faceLAB™ 5 Specifications” which is incorporated herein byreference). Eye position, eye rotation, eye gaze position againstscreen, pupil diameter and eye vergence distance may be monitored. Eyerotation measurements of up to +/−45 degrees around the y-axis and +/−22degrees around the x-axis are possible. Typical static accuracy of gazedirection measurement is 0.5-1 degree rotational error. The gazetracking system includes software and circuitry forming a part of gazesignal processor (in eye interrogation system 900; the processingcapability of computer 908 may also be used, through special purposesoftware or hardware installed therein) to analyze the gaze trackingdata and to detect alignment of the user's gaze with an broad spectrumlight source (interrogation signal source) 914 and/or an opticalcollector/spectrometer (response signal sensor) 916. Alignment of theuser's eyes with the interrogation signal source 914 or the responsesignal sensor 916 triggers activation of the interrogation signal 914source by the circuitry in system 900.

An interrogation signal source 914 and response signal sensor 916 areincorporated in eye interrogation system 900 to determine healthparameters of the computer user. Interrogation signal source 914includes a light source which generates broad spectrum light(approximate wavelengths: 360 nm to 900 nm) located in the interrogationsystem to deliver light to the eye. For example a tungsten halogen lightsource with a wavelength range of 360 nm to 2000 nm in wavelength isavailable from Ocean Optics, Dunedin, Fla. See e.g., the SpecificationSheet: “HL-2000 Tungsten Halogen Light Sources” which is incorporatedherein by reference. Light from the source strikes the cornea, reflectsoff the iris and passes through the anterior chamber of the eye whichcontains aqueous humor with bioanalytes. Methods and systems foranalyzing reflected light to determine bioanalytes in the eye aredescribed (see e.g., U.S. Patent Appl. No. 2011/0184262 by Menonpublished on Jul. 28, 2011 which is incorporated herein by reference).Light reflected from the eye is detected by a response signal sensor 916which is also located in the system (See FIG. 2). The response signalsensor 916 may include an optical collector and a spectrometer todetermine the reflected spectrum. For example the collector may be acollimating lens assembly with a single aspheric lens with a field ofview of approximately 45 degrees (e.g., a 74-DA Collimating Lens(200-2000 nm) is available from Ocean Optics, Dunedin, Fla.). The lensattaches to a spectrometer for increased light throughput and collectscollimated light in a straight path of open air and focuses it on to aspectrometer's slit. The spectrometer may be a fiber optic spectrometerwith a CCD-array detector and an analog to digital converter withprogrammable electrical circuitry. For example a miniature fiber opticspectrometer with a 2048-element CCD-array detector with a range of200-1100 nm and a grating with a spectral range of 625 nm with bestefficiency from 530 nm to 1100 nm is available from Ocean Optics,Dunedin, Fla. (see e.g., the Specification Sheet: USB2000+ MiniatureFiber Optic Spectrometer which is incorporated herein by reference). Thespectrometer has a microcontroller and USB connector to allow activationand programming of the spectrometer by computer 908, usingsoftware/hardware installed therein. To summarize, when the gazetracking system detects alignment of the user's eyes, the signalprocessing circuitry activates the interrogation signal source 914 andthe response signal sensor 916 (spectrometer) to collect data from theuser's eyes.

Health parameters for subject 906 are routinely monitored during use ofthe computer to provide information to subject 906 for example.Information regarding the subject's health parameters may also beprovided to a health care provider or other party, for example via theinternet. The interrogation system may monitor analytes present in theanterior chamber of the eye, for example, sodium salts, glucose,proteins, lipids and other metabolites. For example the concentration ofsodium salts in the aqueous humor in the anterior chamber of the eye maybe determined by reflectance spectroscopy and reference to a spectrumfrom a healthy subject with blood sodium levels in the normal range.Computer algorithms to determine sodium salt concentration based onreflection spectra are described (see e.g., U.S. Patent Appl. No.2011/0184262, Ibid.). For example, user reflectance spectra are comparedwith reference spectra to compute analyte concentration. Multivariateanalysis, e.g., Least Square analysis, may be used to calibrate thereference data and evaluate analyte concentrations. Sodium saltconcentrations in aqueous humor of the eye may be correlated with bloodsodium levels and hydration. To measure glucose levels of the subjectreflectance spectra are obtained for concentrations of glucose as afunction of wavelength. The intensity of light measured at a specificwavelength and the ratio of intensities at two or more wavelengths arecharacteristic for glucose in the aqueous humor of the eye. Acharacteristic pattern for glucose solutions at different wavelengths(e.g., 400 nm to 600 nm) may be established in vitro with the eyeinterrogation system, and an algorithm may be used to determine theconcentration of glucose present in the aqueous humor of the eye.Noncontact optical systems to measure glucose in the eye including:energy sources emitting wavelengths in the visible and near-infraredregions of the spectrum; reflectance detectors, e.g., spectrometers, andcomputer algorithms to analyze spectral data have been described (seee.g., Patent Application No. 2011/0184262, Ibid. and U.S. Pat. No.5,433,197 issued to Stark on Jul. 18, 1995 is incorporated herein byreference). Glucose concentrations in the anterior chamber of the eyeare correlated with blood glucose levels and since the aqueous humor iscontinuously replaced, changes in blood glucose concentrations arereflected in the aqueous humor with a delay of approximately 10 minutes(see e.g., U.S. Pat. No. 5,433,197, Ibid.). Eye interrogation may beused to monitor the computer user's glycemic control. For example, theeye interrogation system may routinely monitor glucose levels in the eyeand alert the user when hyperglycemia is evident.

To monitor the subject's heart rate, the eye interrogation systemincludes an ultrasound system to measure ocular pulse. Ocular pulsationresults from pulsatile blood flow in vasculature of the eye and reflectsheart rate. Systolic heartbeat results in pulsatile ocular blood flowwhich generates a pressure wave at the retina which is transmittedthrough the intraocular media to the cornea which distends, moving 1-50microns and then reverts back to its original position during thediastolic portion of the heartbeat. To measure ocular pulse the eyeinterrogation system includes an ultrasound wave source 918 and areceiver 920 to measure movement of the cornea based on Dopplerfrequency shift (see e.g., U.S. Pat. No. 3,948,248 issued to Zuckermanet al. on Apr. 6, 1976, which is incorporated herein by reference). Forexample the ultrasound source may be a piezoelectric-based transducerthat produces a continuous ultrasonic wave at approximately 1 MHzfrequency which is collimated into a beam 2 mm to 3 mm in diameter thatis focused on the cornea. Ultrasonic waves are reflected from the movingcornea and detected by a receiver 920 which converts the ultrasonicenergy into an electrical signal that is processed by demodulationcircuitry to reduce noise, amplify the signal and determine thefrequency shift (a.k.a., the Doppler shift) of the reflected ultrasoundwaves. The frequency shift of the reflected ultrasound waves is used tocalculate the movement, i.e., pulsation, of the cornea with respect totime, and the velocity of movement versus time is used to calculateheart rate. The relationship between ocular pulse and heart rate aredescribed by linear equations (see e.g., Saha et al., Stroke 24:1686-1690, 1993 which is incorporated herein by reference). A plot ofocular pulsation velocity versus time correlates with a simultaneouselectrocardiogram (see e.g., U.S. Pat. No. 3,948,248 Ibid.). Heart ratesare determined by eye interrogation with ultrasound waves andtransmitted to a computer for storage and comparison to average valuesfor the computer user. Abnormal heart rate is reported to the computeruser. Moreover, ocular pulsation data may be used to identify otherdiseases. For example, ocular pulse distortions may indicate: carotidstenosis, potential stroke and glaucoma. The eye interrogation systemmay alert the computer user when ocular pulsation data indicatepotential diseases exist.

To monitor the computer user's temperature the eye interrogation systemmay include an infrared thermometer which remotely measures temperaturein the eye. An infrared thermometer 922 comprised of a detector,collecting optical system, e.g., lens and filter and processingcircuitry is incorporated in the eye interrogation system. The filterlimits the spectrum of infrared radiation that is detected, and the lensoptical characteristics determine the target size within the eye and theallowed distance from the user's eye. The detector converts infraredenergy into an electrical signal which is amplified and processed by theassociated computer with programs to calculate temperature of the eye.An infrared thermometer suitable for sensitive temperature measurement(i.e., approximately 0.1 degree Centigrade) that may be targeted to theiris/pupil region or to the sclera is described (see e.g., U.S. Pat. No.5,115,815 issued to Hansen on May 26, 1992 which is incorporated hereinby reference). For example an infrared camera may be used to measurecorneal temperature (see e.g., Kessel et al., InvestigativeOphthalmology and Visual Science 51: 6593-6597, 2010 which isincorporated herein by reference). An infrared camera with a focal planearray detector, thermal sensitivity ≦0.09 degrees C. and an accuracy of0.1 degrees C. is available from Fluke Corp., Everett, Wash. (see e.g.,Fluke_Ti25 Datasheet which is incorporated herein by reference). Thegaze tracking system (see above) detects alignment of the infraredthermometer's detector with the user's eye and activates the infraredthermometer. Temperature readings are stored in the computer associatedwith the eye interrogation system and the user may be alerted whentemperature at the eye is above or below the normal range relative tothe ambient temperature (see e.g., Kessel et al., Ibid.). Signalprocessing may be performed in eye interrogation system 900, and/or incomputer 908. For example, physiological parameter values may also besent to computer 908 for data analysis, storage, reporting, and/ortransmission to another party (e.g. a medical caregiver). Accordingly,system 900 permits blood glucose, heart rate, and temperature of subject906 to be measured unobtrusively while subject 906 uses computer 908.

In some embodiments, signal processing circuitry is packaged separatelyfrom signal sources and sensors. Signal processing circuitry (which mayinclude hardware or software) is readily reconfigurable for use withdifferent types and/or numbers of signal sources and sensors, e.g. formeasuring different physiological parameters. A user (either the subjector a caregiver, for example) thus has the option to configure the systemas desired for a specific application.

FIG. 10 depicts a system 1000 for controlling the sensing of informationfrom an eye 102 of a subject 104, which includes signal processingcircuitry 1002 including a gaze signal input 1004 adapted to receive agaze signal 1006 containing information indicative of a gaze directionof the eye 102 of subject 104 sensed from at least an eye 102 of thesubject; a response signal input 1008 adapted to receive a responsesignal 1010 sensed from the eye 102 of the subject 104 by a responsesignal sensor 114 responsive to delivery of an interrogation signal 112to the eye 102 of the subject 104; a gaze signal processor 1012configured to determine the gaze direction 1014 of the eye of thesubject based upon the gaze signal 1006; an alignment detector 1016configured to determine whether the eye of the subject is in alignmentwith respect to at least one of the interrogation signal source 110 orthe response signal sensor 114 based at least in part upon the gazedirection; and a response signal processor 1018 configured to processthe response signal 1010 sensed from the eye 102 of the subject 104 bythe response signal sensor 114 when the eye of the subject is inalignment with respect to the at least one of the interrogation signalsource 110 or the response signal sensor 114 to determine aphysiological parameter 126 from the response signal.

As can be seen from FIG. 10, system 1000 is used in combination with atleast gaze signal sensor 106, interrogation signal source 110, andresponse signal sensor 114. System 1000, used in combination with theseadditional components, provides functionality similar to that offered bysystem 100 as depicted in and described in connection with FIG. 1, forexample. System 1000 is adapted for use in a system including modularcomponents.

System 1000 can include interrogation signal control circuitry 1018configured to drive production of the interrogation signal 112 byinterrogation signal source 110.

System 1000 can include gaze tracking stimulus control circuitry 1020configured to drive production of a gaze tracking stimulus 152 by a gazetracking stimulus source 1022. In an embodiment, gaze tracking stimuluscontrol circuitry 1020 is configured to drive production of a gazetracking stimulus by a plurality of gaze tracking stimulus sources.Response signal processor 1018 may be adapted to process a responsesignal 1010 sensed from an interior of the eye of the subject responsiveto the interrogation signal, e.g., from a lens, aqueous humor, vitreoushumor, or retina of the eye of the subject, as discussed in connectionwith FIG. 2. Response signal processor 1018 may be configured to processthe response signal to determine a feature of the vasculature of the eyeof the subject or a biometric identification of the subject, asdiscussed herein above.

The gaze signal input and the response signal input be may separateinputs, as depicted in FIG. 10, or the same input, as depicted in FIG.11. FIG. 11 depicts a system 1100 in which a single signal source isused as a combined gaze tracking stimulus source/interrogation signalsource 1108, driven by gaze tracking stimulus control circuitry 1106 anda single sensor is used as gaze signal sensor/response signal sensor1114. Gaze signal/response signal 1112 is produced by eye 102 of subject104 in response to gaze tracking stimulus/interrogation signal 1110. Thesensed response signal 1104 is directed to gaze signal processor 1116and response signal processor 1118, which along with alignment detector1120 and gaze tracking stimulus control circuitry 1106, are componentsof signal processing circuitry 1102. Physiological parameter 1122 isdetermined by Response Signal Processor 1118.

FIG. 12 depicts a system 1200, signal processing circuitry 1202 in whichgaze signal input 1204 is adapted to receive a signal from a gaze signalsensor 1206. In related embodiments, signal processing circuitry 1202includes a plurality of gaze signal inputs, e.g., 1204, 1208, and 1210,adapted to receive a plurality of gaze signals 1212, 1214, and 1216containing information indicative of a gaze direction of the eye of thesubject 104 sensed from at least an eye of the subject, from a pluralityof gaze signal sensors 1206, 1218, and 1220.

In an embodiment, response signal processor 1222 is configured toprocess a response signal by determining a first response signal 1224 ata first polarization, determining a second response signal 1226 at asecond polarization, and comparing the response signal 1224 determinedat the first polarization to the response signal 1226 determined at thesecond polarization with comparator 1228, wherein the first polarizationand the second polarization are different. Response signal processor1222 may be configured to process the response signal sensed from theeye of the subject by the response signal sensor when the eye of thesubject is in alignment with respect to the at least one of theinterrogation signal source 110 or the response signal sensor 1222 todetermine, for example, a measurement of oxygenation, blood glucose,heart rate, glycosylated hemoglobin, temperature (e.g., bodytemperature), blood flow, a substance in the eye of the subject, orother physiological parameters as discussed elsewhere herein, from theresponse signal.

In an embodiment, system 1200 includes interrogation signal controlcircuitry 1230. Interrogation signal control circuitry 1230 may beconfigured to drive production of a pulsed interrogation signal byinterrogation signal source 110, as described in connection with FIG. 6.Signal processing circuitry 1202 may be configured to gate detection ofthe response signal (e.g. 1224 or 1226) relative to the pulsedinterrogation signal. Signal processing circuitry 1202 may be configuredto combine multiple response signals produced by the eye of the subjectin response to multiple pulses of the pulsed interrogation signal, e.g.by summing or averaging the multiple response signals, or by determininga moving average or weighted sum of the multiple response signals, asillustrated and discussed in connection with FIG. 6.

In an embodiment, interrogation signal control circuitry 1230 may beconfigured to drive production of a first interrogation signal having afirst optical wavelength and production of a second interrogation signalhaving a second optical wavelength, as described in connection with FIG.8. System 1200 may be used with two or more interrogation signalsources, e.g. 110 and 1232 as shown in FIG. 12. As Signal processingcircuitry 1202 may be configured to process a first response signalsensed from the eye of the subject in response to the firstinterrogation signal and a second response signal sensed from the eye ofthe subject in response to the second interrogation signal by comparingthe first and second response signals in order to determine thephysiological parameter, e.g. with comparator 1228. Signal processingcircuitry 1202 may be configured to drive production of the firstinterrogation signal simultaneously or sequentially with respect to thesecond interrogation signal.

System 1200 may include an output structure 810 adapted to output asignal relating to the determined physiological parameter. The outputstructure can include, e.g., a data transmission structure 812, a datastorage structure 814, a display 816, an audio output 818, or a visualoutput 820, as described in connection with FIG. 8. The system caninclude a display adapted to display information relating to thedetermined physiological parameter. The system can include one ormultiple output structures, to permit one or more signals relating tothe determine physiological parameter to be used for various purposes,such as providing feedback directly to the subject (in various formats,such as numerical, graphical, or narrative), reporting to a medical caregiver or institution, sending information to a data storage device,which may be local or remote, or to a computer network, where it may beaccessed by various parties.

FIG. 13 depicts several examples of systems in which various componentsare packaged in a housing suitable for use in combination with aconventional display device such as, for example, a computer. System1300 is depicted in schematic form, including a housing 1302; aninterrogation signal source 1304 housed in the housing 1302 and adaptedfor delivering an interrogation signal to an eye of a subject, theinterrogation signal source 1304 including at least one light source1308 and at least one optical system 1310; response signal sensor 1312housed within housing 1302 and adapted for sensing a response signalproduced by the eye of the subject responsive to the interrogationsignal, the response signal containing information regarding aphysiological parameter of the subject; output structure 1320 adaptedfor transmitting an output signal; mounting means 1324 adapted formounting housing 1302 with respect to a display in such a manner thatthe interrogation signal source 1304 and response signal sensor 1312 arealignable with the eye of the subject during normal use of the displayby the subject.

In various embodiments, housing 1302 has a size and configuration thatpermits it to be conveniently attached to or otherwise positioned withrespect to an existing device incorporating a display, e.g. atelevision, computer (including but not limited to a desktop, laptop, ortablet computer), telephone, or various displays as described hereinabove. For example, in FIG. 13, housing 1302 a is configured to mount toa telephone 1330 by fitting around it in the same manner as aconventional telephone case. Interrogation signal source 1304 a andresponse signal sensor 1312 a are positioned in housing 1302 a. Inanother example, housing 1302 b is configured to mount to computerdisplay 1332 by means of clips 1324 b that serve as mounting means.

In an aspect, mounting means 1324 (see examples 1324 a and 1324 b) isadapted for mounting the housing 1302 with respect to the display suchthat during normal use of the display by the subject, the interrogationsignal source 1304 (see examples 1304 a and 1304 b) and response signalsensor 1312 (see examples 1312 a and 1312 b) are positioned within thevisual field of at least one eye of the subject. In an aspect, mountingmeans 1324 (see examples 1324 a and 1324 b) is adapted for mounting thehousing 1302 with respect to the display such that the interrogationsignal source and response signal sensor are oriented in substantiallythe same direction as the display surface of the display (see displaysurface 1334 of computer display 1332, and display surface 1336 oftelephone 1330). Mounting means 1324 can be any of a variety of mountingmeans well known to those skilled in the art and can be adapted for usewith a particular types of display. For example, mounting means caninclude one or more clamps, clips, brackets, screws, adhesives, hook andloop strips, pegs, tongue and groove structures, tab and slotstructures, to name a few examples.

As depicted in FIG. 13, system 1300 can include a gaze signal sensor 106adapted for receiving a gaze signal containing information indicative ofa gaze direction of an eye of the subject. Gaze signal sensor caninclude an optical sensor, or optical sensor array, which may includefor example, camera and/or a plurality of gaze signal sensors, asdepicted in and described in connection with FIG. 1, for example.

System 1300 may also include at least one gaze tracking stimulus source150 adapted to deliver a gaze tracking stimulus to at least an eye of asubject, wherein the gaze signal is produced in response to the gazetracking stimulus, as described in connection with FIG. 1. The gazetracking stimulus source 150 may include an infra-red source; inconnection therewith, the gaze signal sensor may include an infra-redsensor. Gaze tracking stimulus source 150 may include a near infra-redsource; in connection therewith, the gaze signal sensor may include anear infra-red sensor. Gaze tracking stimulus source 150 can include oneor a plurality of light sources.

Response signal sensor 1312, which includes light sensor 1314 andoptical system 1316, may be adapted to sense a response signal fromvarious portions of the eye of the subject responsive to theinterrogation signal; e.g., from an interior of the eye, lens, aqueoushumor, vitreous humor, or retina of the eye of the subject responsive tothe interrogation signal. Gaze signal sensor and the response signalsensor can be the same sensor or different sensors, e.g. as shown inFIG. 3. Gaze signal sensor may include an infrared camera, and/or a CCDcamera.

Various combinations of interrogation signal source 1304 and responsesignal sensor 1312 can be used in the various embodiments, as describedherein above. Suitable combinations include, but are not limited to, aninterrogation signal source 1304 that includes a broad spectrum lightsource and a response signal sensor 1312 that includes a spectrometerbased on a CCD array; interrogation signal source 1304 that includes anear-infrared light source and response signal sensor 1312 that includesa near-infrared camera; interrogation signal source 1314 that includes atunable laser source and response signal sensor 1312 that includes aRaman spectrometer based on a CCD camera; interrogation signal source1304 that includes a mid-infrared light source and response signalsensor 1312 that includes a mid-infrared detector; or interrogationsignal source 1304 that includes a tunable laser source and responsesignal sensor 1312 that includes a broad spectrum pyroelectric detector.

The interrogation signal source 1304 may be adapted to produce lighthaving a first polarization, with the response signal sensor is adaptedto detect light having a second polarization, where the firstpolarization and the second polarization are the same, or,alternatively, where the first polarization and the second polarizationare different, as shown in FIG. 12. This may be useful, for example, ifdetection of the physiological parameter is based on detection of achange in polarization caused by the presence (or absence) of a materialof interest.

In various embodiments, the physiological parameter can be a measurementof oxygenation, blood glucose, heart rate, glycosylated hemoglobin,temperature, (e.g., a body temperature), blood flow, a substance in theeye of the subject, or various other physiological parameters asdescribed herein above. As noted previously, the response signal may beindicative of a feature of the vasculature of the eye of the subject ora biometric identification of the subject.

System 1300 can be modified so that the interrogation signal source isadapted to deliver a pulsed interrogation signal, as depicted generallyin FIG. 6. The response signal sensor 1312 may be configured to gatedetection of the response signal relative to the pulsed interrogationsignal. In an embodiment, system 1300 includes signal processingcircuitry 1350 adapted to process the response signal. In one aspect,interrogation signal source 1304 is adapted to deliver a pulsedinterrogation signal, and signal processing circuitry 1350 is configuredto gate detection of the response signal relative to the pulsedinterrogation signal. Signal processing circuitry 1350 includes hardwareand/or software located in housing 1302, or, alternatively, or inaddition, in an external data processing device 1352 (for examplecomputer 1326 b or phone 1330) or in one or more remote locations(represented by network 1340) or distributed across multiple suchlocations. Signal processing circuitry 1350 may be configured to combinemultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal. For example, thesignal processing circuitry may be configured to combine the multipleresponse signals by summing the multiple response signals or averagingthe multiple response signals, or by determining a moving average orweighted sum of the multiple response signals.

As in other embodiment described herein, e.g. as described in connectionwith FIG. 7, in an aspect, the interrogation signal source 1304 isadapted to deliver an interrogation signal containing multiplewavelengths of light. System 1300 may include at least a first responsesignal sensor configured to sense a first response signal produced bythe eye of the subject responsive to a first wavelength component of theinterrogation signal, and a second response signal sensor configured tosense a second response signal produced by the eye of the subjectresponsive to a second wavelength component of the interrogation signal.In an aspect, the system includes at least a first interrogation signalsource configured to deliver a first interrogation signal having a firstoptical wavelength and at least a second interrogation signal sourceconfigured to deliver a second interrogation signal having a secondoptical wavelength. Signal processing circuitry 1350 can be configuredto process a first response signal sensed from the eye of the subject inresponse to the first interrogation signal and a second response signalsensed from the eye of the subject in response to the secondinterrogation signal by comparing the first and second response signalsto determine the physiological parameter. System 1300 can be configuredto deliver the first interrogation signal simultaneously with respect tothe second interrogation signal, or sequentially with respect to thesecond interrogation signal. Interrogation signal source 1304 andresponse signal sensor 1312 can be co-aligned, or in another embodiment,interrogation signal source 1304 and response signal sensor 1312 can beseparately aligned and located.

System 1300 includes output structure 1320, which may include, forexample, a data transmission structure 1360, a serial port 1362, aparallel port 1364, an electromagnetic transmission means 1366, or anoptical transmission means 1368. Output structure 1320 may be adapted totransmit an output signal to the display 1354 (for example computerdisplay 1332 or telephone display 1336), or to a data processing device1352 (which may be computer 1326, for example), wherein, for example,the display is controlled by the data processing device. The outputstructure can include an audio output 1370 and/or a visual output 1372.A visual output 1372 can include a display on housing 1302 (e.g., analphanumeric display, a screen, or simply a light emitting diode orother indicator light) in addition to or in alternative to the displayto which housing 1302 is mounted.

Display 1354 (also visual output 1370) can be configured to displayinformation relating to the determined physiological parameter. Display1354 can be a video monitor, computer display, video game display,telephone display, or terminal of a data processing device. Display 1354can be incorporated in a wearable item (e.g., eyewear, headware,jewelry, an article of clothing, a badge, a bandage, an adhesive patch,a wristwatch, a cuff, a sleeve, a wristband, an armband, a helmet, aphysiological support such as a cast or brace, or a wearable apositioning structure configured to surround a portion of the subject).Display 1354 can be incorporated in an article of furniture, an articleof medical or health-care related equipment, an article of exerciseequipment, or a vehicle, for example. Examples of such displays aredescribed in greater detail herein above.

FIG. 14 is a flow chart of a method 1400 of measuring information froman eye of a subject, including delivering an interrogation signal to theeye of the subject with an interrogation signal source at 1402;detecting a response signal from the eye of the subject with a responsesignal sensor at 1404; determining whether the eye of the subject is inalignment with respect to at least one of the interrogation signalsource and the response signal sensor at 1406; and determining aphysiological parameter of the subject from the response signal detectedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor at 1408. Additional variations and expansionsof method 1400 are illustrated in FIGS. 15-20.

In some method embodiments, the physiological parameter is a measurementof a substance in the blood of the subject, as indicated at 1410, and insome embodiments, the physiological parameter is a measurement of asubstance in an aqueous humor of the subject, as indicated at 1412. Thephysiological parameter can be a measurement of oxygen 1413, glucose1414, a salt 1416, a protein 1418, a lipid 1420, a gas 1422 (e.g.oxygen), a hormone 1424, a drug 1426. The physiological parameter can bea pulse rate 1428, a blood flow 1430, or a temperature 1432.

As shown in FIG. 15, a related method 1500 includes determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at one or more set times 1502, at a set timeinterval 1504, and/or according to a programmed schedule 1506. Forexample, the programmed schedule can be personalized for the subject1508. That is, the schedule may be set depending upon the needs ordesires of the subject. In one aspect, the programmed schedule isselected from among at least two pre-programmed schedules based upon atleast one attribute of the subject 1510. For example, several schedulesmay pre-programmed into the system, with each schedule suitable forsubjects having a particular attribute or attributes; e.g., thetemperature of a subject may be monitored at according to a schedulehaving lower sampling rates if the subject is generally healthy, andaccording to a schedule having higher sampling rates if the subject isknown to be sick and/or if a previous high temperature reading has beendetected from the subject. As another example, the schedule for samplingblood glucose may be set depending upon how quickly the subject's bloodglucose is expected to change at different times during a measurementperiod; that is, measurements may be taken more frequently immediatelyafter a meal and less frequently several hours after the meal if it isexpected that blood glucose will change most rapidly immediately after ameal. Sampling more be performed at a higher rate if a new treatmentregimen is being tried than if the subject is using a well-establishedtreatment regimen. Furthermore, the schedule may be selected based onthe subject's current health status, recent activities, or otherattributes which may be entered into the system by the subject or a careprovider or the subject, or sensed with the system. The programmedschedule can be selected from among at least two pre-programmedschedules based upon the physiological parameter 1512.

As shown in FIG. 16, a method 1600 can include various additional steps,such as reporting information regarding the physiological parameter toan interested party 1602, which may be, for example one or more of thesubject, a medical service provider, a family member, a legal guardianor a legal representative 1604. Alternatively, or in addition, themethod can include comparing the physiological parameter determined fromthe response signal to a previous measurement of a physiologicalparameter to determine a physiological trend 1606. The method may thenalso include reporting information regarding the physiological trend toan interested party 1608, which may be, for example one or more of thesubject, a medical service provider, a family member, a legal guardianor a legal representative 1610.

Method 1600 method may include utilizing the physiological parameterdetermined from the response signal to assess an emotional state of thesubject 1612, or alertness of the subject 1614. For example, heart rate,hormone levels, body temperature, and various other physiologicalparameters as described herein can be used to determine aspects of thesubject's emotional state (e.g., nervousness, excitement, relaxation,etc.) or alertness, as is known to those having skill in the relevantarts. The method can include utilizing the physiological parameterdetermined from the response signal in a medical or health-relatedapplication 1616 or in a business or security application 1618, or both.

As shown in FIG. 17, method 1700 may include presenting an input to thesubject 1702 and utilizing the physiological parameter determined fromthe response signal to determine a response of the subject to the input1704. In some aspects, the input includes information 1706 (including,but not limited to, advertising information 1708, marketing researchinformation 1710, print information 1712, or video information 1714). Insome aspects, the input includes an auditory stimulus 1716, a visualstimulus 1718, a tactile stimulus 1720, an olfactory stimulus 1722, agustatory stimulus 1724, a thermal stimulus 1726, a neural stimulus1728, or a drug, a pharmaceutical, anutraceutical, or a nutrient 1730.Physiological response of the subject to advertising information ormarketing research information may be used to assess the subject'sresponse to such information, for example, for product development,marketing purposes or other business purposes. Similarly, response ofthe subject to various other stimulus (auditory, visual, olfactory,gustatory, etc.) may be used to determine whether or not the subject hasa favorable response to the stimulus, which may be useful for marketing,product development or other business purposes. Alternatively,information relating to the subject's response to such stimuli mayindicate a medical condition of the subject, or the subject's responseto treatment, for monitoring or diagnostic purposes.

FIG. 18 illustrates an example of a system that can be used forpresenting stimuli and assessing the response of the subject to stimuliby means of eye interrogation. An eye interrogation system, computermonitor 902 and computer 908 are provided, as depicted in FIG. 8.Interrogation system 900 may be configured to detect one or morephysiological parameters indicative of the response of subject 1800 to astimulus presented by stimulus unit 1802. Presenting an input to subject1800 may include presenting an input to the subjected in an automatedfashion, under the control of and/or with monitoring by electrical orother circuitry (monitoring may include providing an input to a computerreporting delivery of the input to the subject, or receipt of the inputby the subject, which does not necessarily require that the delivery ofthe input is controlled by the computer). For example, “presentinginformation,” which may include presenting print, video, audio,auditory, or visual or graphical information, can be done by displayinginformation on a screen and/or delivering sound via speakers orheadphone (e.g. playing recorded voice, music, sound, etc.). In broadterms, these are considered auditory stimuli and visual stimuli, which,however, are not limited to auditory and visual inputs having anyparticular information content. Visual and auditory stimuli can readilybe presented to a user by via a computer system that includes a displayand speakers, under control of appropriate software. Other types ofstimuli can be presented using special-purpose stimulus units. See e.g.,U.S. Pat. No. 6,053,738 (describing scent, flavor and tactile/texturestimuli), U.S. Pat. No. 6,542,442 (describing scent stimuli), and U.S.Pat. Nos. 8,308,558 and 8,248,217 (describing tactile/haptic stimuli),each of which is incorporated herein by reference). A tactile stimulusmay include, but is not limited to, pressure or vibration, (e.g.delivered via a probe or air puff), or electrical or electromechanicalstimulation, for example. An olfactory stimulus may include delivery orrelease of an odorant, while a gustatory stimulus may include deliveryor release of a flavoring agent, or provision of a food or otherflavored item. Thermal stimuli can be delivered via a beam of light orother electromagnetic energy, by application of a heated probe, ordelivery of heated air or water. A neural stimulus can be, for example,an electrical, magnetic, or electromagnetic stimulus delivered withimplanted or external (transcutaneous) stimulator. A drug,pharmaceutical, nutraceutical, or a nutrient can be delivered in acontrolled fashion via an implanted or external controlled deliverydevice. Delivery/release of a stimulus may be via one or more stimulusdelivery devices controlled by electrical circuitry (or other types ofcircuitry, e.g. optical circuitry, electromechanical devices, etc.);alternatively, delivery of a stimulus may include action of a human(including the subject) delivering a stimulus to the subject inaccordance with the method. The timing of delivery of a human-deliveredstimulus can be controlled by delivering a computer- or other electricalcircuitry-controlled prompt for the stimulus to be delivered, or byreceiving an input indicating delivery of the stimulus via a user-inputto a computer or other electrical circuitry (e.g. by depressing a buttonor switch, providing an input via a mouse, keyboard, or microphone, orvia other input devices as are known to those skilled in the art).

As shown in FIG. 19, in one aspect, a method 1900 includes, deliveringan interrogation signal to the eye of the subject with an interrogationsignal source and detecting a response signal from the eye of thesubject with a response signal sensor are performed unobtrusively 1902.It is contemplated that performance of the methods as described hereincan be done unobtrusively, e.g., that the measurement of informationfrom the eye of a subject does not appreciably interfere with thesubject's activities, and does not require or elicit any appreciableeffort or attention from the subject. In some embodiments a method maybe considered unobtrusive even if a modest level of effort or attention(either conscious or subconscious) is required of the subject. In someembodiments, delivering an interrogation signal to the eye of thesubject with an interrogation signal source and detecting a responsesignal from the eye of the subject with a response signal sensor areperformed without detection (i.e. without conscious detection and/orwithout subconscious detection) by the subject 1904. For example, ifdetection is performed for medical monitoring purposes, the subject mayrequest or authorize performance of detection. It may be more convenient(or, in some cases more accurate information may be obtained) if thedetection is performed unobtrusively or without detection by thesubject. In some applications, e.g. monitoring of a public space such asa government building or airport, or in various private spaces such as aplace of employment, monitoring may be performed to detect health orsecurity risks, and subjects may be informed that monitoring will takeplace, although the actual taking of measurements may be unobtrusive orundetectable to the subject.

In some embodiments it may be desired to perform the methodunobtrusively and/or without detection by the subject (at the time themeasurement is being made) but to notify the subject about theperformance of the method, or perform the method at the request of orwith the consent of the subject. For example, the method may includereceiving an input indicative of an instruction from the subject orrepresentative of the subject for information to be measured 1906,receiving an input indicative of authorization from the subject orrepresentative of the subject for information to be measured 1908, orreceiving an input indicative of informed consent from the subject orrepresentative of the subject for information to be measured 1910.

As shown in FIG. 20, in an embodiment, method 2000 includes transmittingat least one of information regarding the subject, information regardingthe system used for determining the physiological parameter, orinformation regarding the physiological parameter to a data processingsystem 2002. In embodiment the method includes receiving at least one ofinformation regarding the subject, information regarding the system usedfor determining the physiological parameter, or information regardingthe physiological parameter from a data processing system 2004. In anembodiment, the method includes sharing at least one of informationregarding the subject, information regarding the system used fordetermining the physiological parameter, or information regarding thephysiological parameter between two of more data processing systems2006.

In an aspect, the method includes determining the identity of thesubject 2008. Determining the identity of the subject may be done, e.g.,through the use of facial recognition 2010, through the use of retinalrecognition 2012, or by determining the identity of the subject bycomparing login information entered by the subject with logininformation in a registry 2014, by methods known to those having skillin the relevant arts. In an aspect, delivering the interrogation signalto the eye of the subject with the interrogation signal source can bedone only when the identity of the subject meets a selection criterion,as indicated at 2016; for example, once the identity of the subject hasbeen determined, the identity of the subject may be compared with anidentity of one or more approved subjects, and if the identity matchesan identity of an approved subject, the selection criterion is met andthe interrogation signal is delivered.

In various embodiments, methods as described herein may be performedaccording to instructions implementable in either hardware, software,and/or firmware. Such instructions may be stored in non-transitorymachine-readable data storage media, for example. Those having skill inthe art will recognize that the state of the art has progressed to thepoint where there is little distinction left between hardware, software,and/or firmware implementations of aspects of systems; the use ofhardware, software, and/or firmware is generally (but not always, inthat in certain contexts the choice between hardware and software canbecome significant) a design choice representing cost vs. efficiencytradeoffs. Those having skill in the art will appreciate that there arevarious vehicles by which processes and/or systems and/or othertechnologies described herein can be effected (e.g., hardware, software,and/or firmware), and that the preferred vehicle will vary with thecontext in which the processes and/or systems and/or other technologiesare deployed. For example, if an implementer determines that speed andaccuracy are paramount, the implementer may opt for a mainly hardwareand/or firmware vehicle; alternatively, if flexibility is paramount, theimplementer may opt for a mainly software implementation; or, yet againalternatively, the implementer may opt for some combination of hardware,software, and/or firmware in one or more machines, compositions ofmatter, and articles of manufacture, limited to patentable subjectmatter under 35 USC 101. Hence, there are several possible vehicles bywhich the processes and/or devices and/or other technologies describedherein may be effected, none of which is inherently superior to theother in that any vehicle to be utilized is a choice dependent upon thecontext in which the vehicle will be deployed and the specific concerns(e.g., speed, flexibility, or predictability) of the implementer, any ofwhich may vary. Those skilled in the art will recognize that opticalaspects of implementations will typically employ optically-orientedhardware, software, and or firmware. In some implementations describedherein, logic and similar implementations may include software or othercontrol structures. Electronic circuitry, for example, may have one ormore paths of electrical current constructed and arranged to implementvarious functions as described herein. In some implementations, one ormore media may be configured to bear a device-detectable implementationwhen such media hold or transmit device detectable instructions operableto perform as described herein. In some variants, for example,implementations may include an update or modification of existingsoftware or firmware, or of gate arrays or programmable hardware, suchas by performing a reception of or a transmission of one or moreinstructions in relation to one or more operations described herein.Alternatively or additionally, in some variants, an implementation mayinclude special-purpose hardware, software, firmware components, and/orgeneral-purpose components executing or otherwise invokingspecial-purpose components.

Implementations may include executing a special-purpose instructionsequence or invoking circuitry for enabling, triggering, coordinating,requesting, or otherwise causing one or more occurrences of virtuallyany functional operations described herein. In some variants,operational or other logical descriptions herein may be expressed assource code and compiled or otherwise invoked as an executableinstruction sequence. In some contexts, for example, implementations maybe provided, in whole or in part, by source code, such as C++, or othercode sequences. In other implementations, source or other codeimplementation, using commercially available and/or techniques in theart, may be compiled//implemented/translated/converted into a high-leveldescriptor language (e.g., initially implementing described technologiesin C or C++ programming language and thereafter converting theprogramming language implementation into a logic-synthesizable languageimplementation, a hardware description language implementation, ahardware design simulation implementation, and/or other such similarmode(s) of expression). For example, some or all of a logical expression(e.g., computer programming language implementation) may be manifestedas a Verilog-type hardware description (e.g., via Hardware DescriptionLanguage (HDL) and/or Very High Speed Integrated Circuit HardwareDescriptor Language (VHDL)) or other circuitry model which may then beused to create a physical implementation having hardware (e.g., anApplication Specific Integrated Circuit). Those skilled in the art willrecognize how to obtain, configure, and optimize suitable transmissionor computational elements, material supplies, actuators, or otherstructures in light of these teachings.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by those within the art that each function and/or operationwithin such block diagrams, flowcharts, or examples can be implemented,individually and/or collectively, by a wide range of hardware, software,firmware, or virtually any combination thereof, limited to patentablesubject matter under 35 U.S.C. §101. In an embodiment, several portionsof the subject matter described herein may be implemented viaApplication Specific Integrated Circuits (ASICs), Field ProgrammableGate Arrays (FPGAs), digital signal processors (DSPs), or otherintegrated formats. However, those skilled in the art will recognizethat some aspects of the embodiments disclosed herein, in whole or inpart, can be equivalently implemented in integrated circuits, as one ormore computer programs running on one or more computers (e.g., as one ormore programs running on one or more computer systems), as one or moreprograms running on one or more processors (e.g., as one or moreprograms running on one or more microprocessors), as firmware, or asvirtually any combination thereof, limited to patentable subject matterunder 35 U.S.C. §101, and that designing the circuitry and/or writingthe code for the software and or firmware would be well within the skillof one of skill in the art in light of this disclosure. In addition,those skilled in the art will appreciate that the mechanisms of thesubject matter described herein are capable of being distributed as aprogram product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of signal bearing medium used to actually carry outthe distribution. Examples of a signal bearing medium include, but arenot limited to non-transitory machine-readable data storage media suchas a recordable type medium such as a floppy disk, a hard disk drive, aCompact Disc (CD), a Digital Video Disk (DVD), a digital tape, acomputer memory, etc. A signal bearing medium may also includetransmission type medium such as a digital and/or an analogcommunication medium (e.g., a fiber optic cable, a waveguide, a wiredcommunications link, a wireless communication link (e.g., transmitter,receiver, transmission logic, reception logic, etc), etc.).

FIG. 21 illustrates in schematic form an article of manufacture 2100that includes one or more non-transitory machine-readable data storagemedia 2102 bearing one or more instructions 2104 for delivering aninterrogation signal to an eye of the subject with an interrogationsignal source; detecting a response signal from the eye of the subjectwith a response signal sensor; determining whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor; anddetermining a physiological parameter of the subject from the responsesignal detected from the eye of the subject when the eye of the subjectis in alignment with respect to the at least one of the interrogationsignal source and the response signal sensor. As discussed herein above,the physiological parameter can be a measurement of a substance in theblood of the subject (e.g. as oxygen, glucose, a salt, a protein, or alipid), a measurement of a substance in an aqueous humor of the subject(e.g., oxygen, glucose, a salt, a protein, or a lipid, a hormone, adrug), or a pulse rate, for example.

The one or more non-transitory machine-readable data storage media 2102can bear one or more instructions 2104 for performing method steps asdepicted in FIG. 15 for determining the physiological parameter of thesubject from the response signal detected from the eye of the subject atone or more set times, one or more instructions for determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at a set time interval, and/or one or moreinstructions for determining the physiological parameter of the subjectfrom the response signal detected from the eye of the subject accordingto a programmed schedule. The programmed schedule can be personalizedfor the subject. The one or more non-transitory machine-readable datastorage media can be bear one or more instructions for selecting theprogrammed schedule from among at least two pre-programmed schedulesbased upon at least one attribute of the subject. For example, the oneor more non-transitory machine-readable data storage media bear one ormore instructions for selecting the programmed schedule from among atleast two pre-programmed schedules based upon the physiologicalparameter.

In an embodiment, the one or more non-transitory machine-readable datastorage media 2102 bear one or more instructions for performing steps ofmethod 1600 as depicted in FIG. 16, for reporting information regardingthe physiological parameter to an interested party, one or moreinstructions for comparing the physiological parameter determined fromthe response signal to a previous measurement of a physiologicalparameter to determine a physiological trend, and may also include oneor more instructions for reporting information regarding thephysiological trend to an interested party. In an embodiment, thearticle of manufacture 2100 includes one or more non-transitorymachine-readable data storage media 2102 bearing one or moreinstructions for utilizing the physiological parameter determined fromthe response signal to assess an emotional state of the subject, or oneor more instructions for utilizing the physiological parameterdetermined from the response signal to assess the alertness of thesubject. The article of manufacture may include one or morenon-transitory machine-readable data storage media that bear one or moreinstructions for utilizing the physiological parameter determined fromthe response signal in a medical or health-related application, or oneor more instructions for utilizing the physiological parameterdetermined from the response signal in a business or securityapplication.

In an embodiment, the article of manufacture 2100 includes one or morenon-transitory machine-readable data storage media 2102 that bear one ormore instructions for performing method 1799 as depicted in FIG. 17,including presenting an input to the subject; and utilizing thephysiological parameter determined from the response signal to determinea response of the subject to the input. In an embodiment, the one ormore non-transitory machine-readable data storage media bear one or moreinstructions for presenting information to the subject, for example,advertising information, marketing research information, printinformation, or video information. In various embodiments, the one ormore non-transitory machine-readable data storage media bear one or moreinstructions for presenting various stimuli to the subject, e.g., anauditory stimulus, a visual stimulus, a tactile stimulus, an olfactorystimulus, a gustatory stimulus, a thermal stimulus, a neural stimulus,or a drug or pharmacologically active substance.

As noted above, the method may be performed unobtrusively or withoutdetection, at the instruction of the subject, or with or without thepermission or notification of the subject. The article of manufacture2100 may include one or more non-transitory machine-readable datastorage media 2102 that bear one or more instructions 2104 for receivingan input indicative of an instruction from the subject or representativeof the subject for information to be measured, receiving an inputindicative of authorization from the subject or representative of thesubject for information to be measured, and/or receiving an inputindicative of informed consent from the subject or representative of thesubject for information to be measured, as depicted in FIG. 19.

In some embodiments, the article of manufacture 2100 may include one ormore non-transitory machine-readable data storage media 2102 that bearone or more instructions for transmitting at least one of informationregarding the subject, information regarding the system used fordetermining the physiological parameter, or information regarding thephysiological parameter to a data processing system, as depicted in FIG.20 at 2002.

In some embodiments, the article of manufacture 2100 may include one ormore non-transitory machine-readable data storage media 2102 that bearone or more instructions for receiving at least one of informationregarding the subject, information regarding the system used fordetermining the physiological parameter, or information regarding thephysiological parameter from a data processing system, as depicted inFIG. 20 at 2004.

In some embodiments, the article of manufacture 2100 may include one ormore non-transitory machine-readable data storage media 2102 that bearone or more instructions for sharing at least one of informationregarding the subject, information regarding the system used fordetermining the physiological parameter, or information regarding thephysiological parameter between two of more data processing systems, asdepicted in FIG. 20 at 2006.

In some embodiments, the article of manufacture 2100 may include one ormore non-transitory machine-readable data storage 2102 media that bearone or more instructions 2104 for determining the identity of thesubject, which may be, for example, instructions for determining theidentity of the subject through the use of facial recognition,determining the identity of the subject through the use of retinalrecognition, and/or determining the identity of the subject by comparinglogin information entered by the subject with login information in aregistry, as depicted in FIG. 20 at 2008-2014.

FIG. 22 depicts a system 2200 for sensing information from an eye 102 ofa subject 104, the system including an interrogation signal source 2202for delivering an interrogation signal 2204 to an eye 102 of a subject104; a response signal sensor 2206 for sensing a response signal 2208produced by the eye of the subject responsive to interrogation signal2204; a gaze signal sensor 2210 adapted for receiving a gaze signal 2212containing information indicative of a gaze direction of an eye 102 ofthe subject 104; at least one actuator 2216, 2218 configured to adjustat least one of the interrogation signal source 2202 or the responsesignal sensor 2206 to bring at least one of the interrogation signalsource 2202 or the response signal sensor 2206 into alignment with theeye 102 of the subject 104; and signal processing circuitry 2220including: a response signal processor 2222 configured to process aresponse signal 2224 sensed from the eye of the subject to determine aphysiological parameter 126 from the response signal, a gaze signalprocessor 2226 configured to determine the gaze direction of the eye ofthe subject based upon the gaze signal 2212; an alignment detector 2232configured to determine whether the eye 102 of the subject 104 is inalignment with respect to at least one of the interrogation signalsource 2202 or the response signal sensor 2206 based at least in partupon the gaze direction; and an actuator controller 2234 configured to:determine a target position for at least one of the interrogation signalsource and the response signal sensor based at least in part on the gazedirection; and generate an actuator control signal 2236 to drive the atleast one actuator 2216, 2218 to adjust at least one of theinterrogation signal source 2202 or the response signal sensor 2206 tobring at least one of the interrogation signal source 2202 or theresponse signal sensor 2206 into alignment with the eye 102 of thesubject 104.

In an embodiment, the system includes a rangefinder 2240 adapted fordetermining the distance between the eye 102 of the subject and theinterrogation signal source 2202 and an autofocus system 2242 forfocusing the interrogation signal source 2202 responsive to thedetermined distance 2244. Alternatively, or in addition, rangefinder2240 may be adapted for determining the distance between the eye of thesubject and the response signal sensor 2206; and an autofocus system2242 may be adapted for focusing the response signal sensor 2206responsive to the determined distance.

In an embodiment, the at least one actuator 2216 is configured to adjustthe interrogation signal source 2202 by adjusting the position of atleast a portion of the interrogation signal source. The interrogationsignal source can include at least one optical component 2244, and theat least one actuator 2216, can be configured to adjust theinterrogation signal source 2202 by adjusting at least one opticalcomponent 2244 of the interrogation signal source.

In an embodiment, the at least one actuator 2218 is configured to adjustthe response signal sensor 2206 by adjusting the position of at least aportion of the response signal sensor 2206. The response signal sensor2206 can include at least one optical component 2246, and the at leastone actuator 2216 can be configured to adjust the response signal sensor2206 by adjusting at least one optical component 2246 of the responsesignal sensor.

Adjusting the position of interrogation signal source 2202 or responsesignal sensor 2206 can include rotational or translation motion of thelight source or sensor, or movement or adjustment of a component thatcan control the position/focal distance of the light beam beinggenerated or sensed (e.g., a mirror, lens, or reflector). In anembodiment, the least one actuator is configured to scan the at leastone of the interrogation signal source 2202 or the response signalsensor 2206 through a region in which the eye of the subject is locatedsuch that the at least one of the interrogation signal source and theresponse signal sensor will be brought into alignment with the eye ofthe subject at at least one position within the scanned region.

Interrogation signal source 2202 and the response signal sensor 2206 canbe co-aligned, or separately aligned and located, as discussed hereinabove.

The system may also include data capture circuitry 2250 configured tocapture a response signal 2224 from the eye of the subject in connectionwith determination by the signal processing circuitry that the eye ofthe subject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor, as indicatedby signal 2252 from alignment detector 2232. Data capture circuitry 2250provides for capture (acquisition and/or storage e.g. in data storage2254) of data obtained while system components are aligned such data maycontain information measured from eye 102 of subject 104.

As shown in FIG. 23, system 2300 may also include a display 2310, whichmay be, for example, a computer display 2312, a telephone display 2314,or a video monitor, a video game display, a terminal of a dataprocessing device (not shown). The display can be incorporated in awearable item, which may be, for example, eyewear, headware, jewelry, anarticle of clothing, a badge, a bandage, an adhesive patch, awristwatch, a cuff, a sleeve, a wristband 2316 (depicted in FIG. 23), anarmband, a helmet, a physiological support such as a cast or brace, or awearable a positioning structure configured to surround a portion of thesubject. The display can be incorporated in an article of furniture, anarticle of medical equipment, an article of health-care relatedequipment, an article of exercise equipment, or a vehicle. Examples ofsuch displays are described in greater detail herein above.

The system 2300 can include electrical circuitry 2320 configured tocause a visual stimulus 2322 to be displayed on the display 2310 toattract the gaze of the subject 104. The electrical circuitry mayinclude at least one of hardware, software, or firmware. In anembodiment, the electrical circuitry 2320 is configured to cause thevisual stimulus 2322 to be displayed at a location on the display 2310such that when the gaze of the subject is directed toward the visualstimulus 2322 the eye 102 of the subject 104 will be brought intoalignment with respect to the at least one of the interrogation signalsource 2202 or the response signal sensor 2206. In various embodiments,the electrical circuitry 2320 is configured to cause a visual stimulus2322 to be displayed on the display 2310 that includes a different lightintensity relative to a visual background, a different opticalwavelength relative to a visual background, a different temporal patternof light intensity or optical wavelength relative to a visualbackground, or a different spatial pattern of light intensity or opticalwavelength relative to a visual background. The electrical circuitry2320 can be configured to cause a visual stimulus 2322 to be displayedon the display that includes any or all of an image, a moving image, ortext. The visual stimulus can include or be displayed in connection withother text and/or graphics displayed on the screen (for example as abutton that the subject must select or click, a text box with text to beread by the subject, or a flashing icon or moving image on the screen).

As an example, FIG. 23 illustrates a wristband 2316 a on the wrist of asubject 104, including gaze signal sensor 2210 a, interrogation signalsource 2202 a, response signal sensor 2206 a and display 2310 a showingvisual stimulus 2322 a. For example, visual stimulus 2322 a can be aflashing image on display 2310 a on wristband 2316 a. Components onwristband 2316 a can be microfabricated/MEMS components. Signalprocessing circuitry associated with armband 2316 a (not depicted) maybe located on wristband 2316 a, or located fully or in part at a remotelocation, operably linked to components on 2316 a via a wirelessconnection.

EXAMPLE 2 An Unobtrusive Eye Interrogation System to Monitor PassengersUpon Check-in at the Airport

FIG. 24 depicts an example of an unobtrusive eye interrogation system2400 that is used for monitoring passenger 2404 upon check-in at anairport. Eye interrogation system 2400, which collects biometric andphysiologic data from passengers, is incorporated in a check-in kiosk2402 at the airport. The system automatically detects the gave ofpassenger 2404 and aligns with his eyes at the computer monitor atcheck-in. The system measures biometric parameters to identify passenger2404 and physiological parameters to screen for stress, nervousness,anxiety and signs of contagious disease. The eye interrogation systemtransmits the passenger's biometric and physiological data 126 tocomputers at the airlines and to airport security. The system alertsairport security and the airlines if the passenger's identificationand/or physiological parameters indicate they may be a potentialsecurity or health risk.

The eye interrogation system 2400 is constructed in association with thecomputer screen 2406 at the check-in kiosk 2402. The system 2400 has anactive gaze alignment system to align the interrogation system and thepassengers'eyes. Gaze tracking system 2408 is used to detect where thepassenger's gaze strikes the computer screen. The gaze tracking systemis comprised of an IR light source (gaze tracking stimulus source 2410)and an IR camera (gaze signal sensor 2412 which detects the reflectionof IR light from the eyes of the passenger. For example, a gaze trackingsystem for monitoring eye position is available from Seeing MachinesInc., Tucson, Ariz. (see e.g., the Specification Sheet: “faceLAB™ 5Specifications” which is incorporated herein by reference). Eyeposition, eye rotation, eye gaze position against screen, pupil diameterand eye vergence distance may be monitored. Eye rotation measurements ofup to +/−45 degrees around the y-axis and +/−22 degrees around thex-axis are possible. Typical static accuracy of gaze directionmeasurement is 0.5-1 degree rotational error. The gaze tracking systemincludes electric circuitry 2414, including e.g. software and hardware,to analyze the reflected IR waves and to determine the position of thepassenger's gaze and the location of the passenger's eyes. Gaze trackingdata 2416 is used by alignment detector 2232 and actuator controller2428 to control actuator (s) 2216 align eye interrogation sources (e.g.2420 a, 2420 b, 2420 c) and sensors (e.g. 2422 a, 2422 b, 2422 c) withthe passenger's eyes. An active alignment system comprised of actuatorsand controllers moves the sources and sensors into alignment with thepassenger's eyes. An actuated optical system to control alignment oflight sources or light sensors with a viewer's eyes is described (seee.g., European Patent Application No. EP 2 508 931 A1 by Oellerspublished on Oct. 10, 2012 which is incorporated herein by reference).Eye location data from the gaze tracking system (see above) is providedto a controller which is programmed to activate linear actuators 2216,2218 to align the eye interrogation sources 2420 a, 2420 b, 2420 c 4 andsensors 2422 a, 2422 b 2422 c with the passenger's eyes. Controllerscapable of motion control in six dimensions and linear actuators areavailable from Newport Corp., Irvine, Calif. (see e.g. the Specificationsheet: Picomotor Piezo Linear Actuators which is incorporated herein byreference). Rapid alignment of the eye interrogation system with thepassenger's eyes is followed by activation of the interrogation sources2420, 2420 b, 2420 c and sensors 2422 a, 2422 b, 2422 c by system 2400.

The eye interrogation system 2400 includes electromagnetic radiationsources and sensors which are contained within the check-in kiosk. Alight source 2424 a for iris scanning and a camera 2422 a to captureiris images is incorporated in the system to identify the passengerchecking in. Systems and algorithms to obtain iris images, identifyunique signatures and rapidly compare key features of iris images to alarge database of iris images are described (see e.g., U.S. Pat. No.5,572,596 issued to Wildes et al. on Nov. 5, 1996 and U.S. Pat. No.4,641,349 issued to Flom et al. on Feb. 3, 1987 which are incorporatedherein by reference). An iris scanning system which includes anear-infrared (approximately 700-900 nm) illumination source, a 1.3megapixel camera and algorithms to analyze and compare iris images isavailable from Bayometric Inc., San Jose, Calif. (see e.g., theSpecification Sheet: “Crossmatch Retinal Scan 2 Iris Scanner” which isincorporated herein by reference). Biometric information obtained by theiris scanner is compared to the passenger's ticket, passport and visainformation, and discrepancies are transmitted to airport securitypersonnel as well as the airlines.

To detect passengers who may be a health risk, e.g., have a feverassociated with an infectious disease, an infrared thermometer 2432 isplaced in the eye interrogation system which remotely measurestemperature in the eye. Following active alignment of the infraredthermometer with the passenger's eye the thermometer is activated. Aninfrared thermometer comprised of a detector, collecting optical system(e.g., lens and filter) and signal processing circuitry (in responsesignal processor 2430) is incorporated in the eye interrogation system.The filter limits the spectrum of infrared radiation detected and thelens' optical characteristics determine the target size within the eyeand the allowed distance from the passenger's eye. The detector convertsinfrared energy into an electrical signal which is amplified andprocessed by the associated signal processors to calculate temperatureof the eye. An infrared thermometer suitable for sensitive temperaturemeasurement (i.e., approximately 0.1 degree Centigrade) that may betargeted to the iris/pupil region or to the sclera is described (seee.g., U.S. Pat. No. 5,115,815 issued to Hansen on May 26, 1992 which isincorporated herein by reference). For example an infrared camera may beused to measure corneal temperature (see e.g., Kessel et al.,Investigative Opthalmology and Visual Science 51: 6593-6597, 2010 whichis incorporated herein by reference). An infrared camera with a focalplane array detector, thermal sensitivity ≦0.09 degrees C. and anaccuracy of 0.1 degrees C. is available from Fluke Corp., Everett, Wash.(see e.g., Fluke_Ti25 Datasheet which is incorporated herein byreference). To summarize, the gaze tracking system (see above) detectsthe passenger's gaze and eye location which are signaled to actuatorswhich align the infrared detector with the passenger's eye. Next thesystem controller activates the infrared thermometer and signalprocessors determine eye temperature. Corneal eye temperatures may becorrelated with body temperatures and ambient temperatures (see e.g.,Kessel et al., Ibid.). Temperature data are stored and analyzed by acomputer associated with the eye interrogation system, and securitypersonnel and the airlines are alerted when temperature in the eye isoutside the normal range and may indicate an infectious disease ispresent.

To identify passengers who may represent other types of risk such asterrorism the eye interrogation system uses a bioanalyte detectionsystem in conjunction with biometric identification, e.g., irisscanning. Unobtrusive, noncontact detection and quantitation ofbiological, metabolites, and chemicals may be done using a remotespectroscopic device to interrogate the passenger's eye and processorsand algorithms to process the spectroscopic signals. For example, aspectroscopic system to obtain Raman spectral data may include a lasersource, spatial filters, a beam splitter, notch filters, confocaloptics, a CCD detector and a low pass electrical filter (see e.g., U.S.Pat. No. 6,961,599 issued to Lambert et al. on Nov. 1, 2005 which isincorporated herein by reference). The eye interrogation source may be atunable laser 2420 b to provide excitation beams of wavelengths fromabout 400 nm to 900 nm (e.g., a tunable external cavity diode laser isavailable from Thorlabs, Newton, N.J.). For example the excitation beammay be at wavelength approximately 785 nm which is barely visible to thepassenger and thus elicits Raman spectra unobtrusively A confocal opticsystem allows one to focus the excitation beam on selected regions ofthe eye, for example, the aqueous humor in the anterior chamber of theeye, or the blood vessels in the conjunctiva or the retina. A CCDdetector 2422 b with high quantum efficiency in the 400-1100 nmwavelength range is used to detect Raman spectra (e.g., a silicon CCDlinear array (Sony 2048) is available from Avantes, Broomfield, Colo.;see “Table 4 Detector Specifications” in “Sensitivity”, Avantes,http://www.avantes.com website, which is incorporated herein byreference).

To identify passengers who are under stress or agitated and who mayrepresent a risk to other passengers, such as that posed by a terrorist,the eye interrogation system may detect “fight or flight hormones”. Whenpassenger 2404 views the check-in monitor, the active gaze alignmentsystem aligns and activates the interrogation source, i.e., the tunablelaser 2420 b, and an excitation beam of approximately 500 nm wavelengthis focused on the blood vessels in the conjunctiva of the passenger'seye. Reflected spectra, including any resonant Raman spectra aredetected by the CCD array 2422 b and transmitted as electronic signalsto the signal processor (response signal processor 2430) of the eyeinterrogation system 2400. Raman spectra which arise from stresshormones are identified by the signal processing software from adatabase of reference Raman spectra for epinephrine, norepinephrine andhydrocortisone in blood. The concentration of stress hormones may bedetermined by signal processing algorithms which correlate emissionspectra intensity with analyte concentration (see e.g., U.S. Pat. No.6,961,599, Ibid.). Passengers with elevated concentrations of stresshormones in their blood may also be tested for elevated heart rate,another indication of stress or agitation.

The eye interrogation system may also use pupillometry to detectpassengers who are under stress and/or a high cognitive load. Data onpupil diameter, mean pupil diameter change (MPDC), and mean pupildiameter change rate (MPDCR) are collected with the gaze tracking system2408 described above (see e.g., a gaze tracking system available fromSeeing Machines Inc., Tucson, Ariz.; the Specification Sheet: “faceLAB™5 Specifications” which is incorporated herein by reference), andparameters determined by signal processing circuitry 2220. Methods andcalculations employing remote imaging to measure MPDC and MPDCR and tomonitor cognitive load are described (see e.g., Klingner, Dissertationsubmitted to Stanford University May 2010: Measuring Cognitive LoadDuring Visual Tasks by Combining Pupillometry and Eye Tracking,available at http://purl.stanford.edu/mv271zd7591 and Palinko et al.,Proceedings of the 2010 Symposium on Eye Tracking Research andApplications pp. 141-144, Austin, Tex. which are incorporated herein byreference). For example, a remote eye tracking system (e.g., Tobii 1750video eye tracker available from Tobi Technology, Inc., Falls Church,Va.) may be used to measure pupil diameters with an accuracy of 0.34 mmand a precision of 0.12 mm. To measure cognitive load multiplemeasurements are made in a time scale of fractions of a second and thechange in pupil diameter at the initiation of a task is averaged overmany repetitions. Mean pupil diameter may vary by approximately 0.1-0.5mm within about 2 seconds after an increase in cognitive load (see e.g.,Klingner, Ibid.). To measure the passenger's cognitive load visual tasksare presented on the video monitor and multiple measurements of pupildiameter are recorded and the MPDC and MPDCR are calculated. Thecorresponding cognitive load and stress level is computed by comparisonto baseline data collected for the passenger and cumulative data formultiple passengers analyzed by the eye interrogation system. Thecalculated cognitive load is compared to other parameters (e.g.,cortisol level, heart rate) and passengers who display abnormal stressparameters are reported to airport security and to airlines personnel.

To monitor the passenger's heart rate and respiration the eyeinterrogation system is equipped with an interferometry system thatdetects movement of an individual's chest wall. Construction of aninterferometer, data acquisition systems and signal processingalgorithms to determine heart rate and respiration are described (seee.g., Mikhelson et al., IEEE Transactions on Biomedical Engineering, 58:1671-1677, 2011 which is incorporated herein by reference). For examplea continuous wave millimeter-wave interferometer is constructed integralto the eye interrogation system. A continuous wave 94-GHz signal isgenerated by a cavity-tuned Gunn diode oscillator 2420 c and transmittedat the computer user with a Gaussian (quasi-optical) antenna with a lensthat results in a far-field starting at approximately 0.5 meter and abeam divergence of approximately 1.5 degrees. The gaze tracking system2408 (see above) is used to infer alignment of the oscillator andantenna on the user's chest and to signal activation of theinterferometer. Interferometer components include: a Gunn diodeoscillator (94 GHz) a circulator, a Gaussian antenna and beam splittersand mixers. To acquire the reflected wave signals (via the antenna), a24 bit data acquisition device 2422 c (DAQ) (e.g., a PCI-4474 DAQavailable from National Instruments, Austin, Tex.; see the Data sheet:“DAQ Device” which is incorporated herein by reference) is used withLabView data acquisition software. The vibration signals may beprocessed with programs written in MATLAB to derive chest displacements(respiration) and heart beats from the reflected wave signals (see e.g.,Mikhelson et al., Ibid.). Heart rate and respiration data areaccumulated and analyzed by computer software and authorities andairline personnel may be alerted when, for example, a passenger's heartrate and/or respiration rate exceeds the normal range.

FIG. 25 depicts a system 2500 for controlling the sensing of informationfrom an eye 102 of a subject 104, including signal processing circuitry2502 including a gaze signal input 2504 adapted to receive a gaze signal2506 containing information indicative of a gaze direction of the eye ofthe subject sensed from at least an eye of the subject; a responsesignal input 2508 adapted to receive a response signal 2510 sensed fromthe eye of the subject by a response signal sensor 2206 responsive todelivery of an interrogation signal 2204 to the eye of the subject; aresponse signal processor 2222 configured to process a response signalsensed from the eye of the subject to determine a physiologicalparameter 216 from the response signal; a gaze signal processor 2226configured to determine the gaze direction of the eye of the subjectbased upon the gaze signal; an alignment detector 2232 configured todetermine whether the eye of the subject is in alignment with respect toat least one of the interrogation signal source 2202 or the responsesignal sensor 2206 based at least in part upon the gaze direction; andan actuator controller 2234 configured to: determine a target positionfor at least one of the interrogation signal source 2202 or the responsesignal sensor 2206 based at least in part on the gaze direction; andgenerate an actuator control signal 2236 to drive the at least oneactuator 2216, 2218 to adjust at least one of the interrogation signalsource 2202 or the response signal sensor 2206 to bring at least one ofthe interrogation signal source 2202 or the response signal sensor 2206into alignment with the eye 102 of the subject 104.

The system may also include interrogation signal control circuitry 2520configured to drive production of the interrogation signal 2204 by aninterrogation signal source 2202.

In an embodiment, the system includes gaze tracking stimulus controlcircuitry 2522 configured to drive production of a gaze trackingstimulus 152 by a gaze tracking stimulus source 150, including, e.g.gaze tracking stimulus control circuitry configured to drive productionof a gaze tracking stimulus by a plurality of gaze tracking stimulussources. In an aspect, the gaze signal input 2504 and the responsesignal input 2508 are separate inputs. In another, the gaze signal input2504 and the response signal input 208 are the same input, as discussedgenerally in connection with, e.g. FIG. 3. The response signal processor2222 may be adapted to process a response signal sensed from an interiorof the eye of the subject responsive to the interrogation signal, e.g.from a lens, aqueous humor, vitreous humor, or retina of the eye of thesubject, as discussed herein above. In an embodiment, the responsesignal processor is configured to process the response signal todetermine a feature of the vasculature of the eye of the subject, and ordetermine a biometric identification of the subject.

Gaze signal input 2504 may be adapted to receive a signal from a camera,for example. In some embodiments, signal processing circuitry 2502includes a plurality of gaze signal inputs (only one is depicted)adapted to receive a plurality of gaze signals containing informationindicative of a gaze direction of the eye of the subject sensed from atleast an eye of the subject.

In an embodiment, response signal processor 2222 is configured toprocess the response signal by determining a first response signal at afirst polarization, determining a second response signal at a secondpolarization, and comparing the response signal determined at the firstpolarization to the response signal determined at the secondpolarization, wherein the first polarization and the second polarizationare different, as discussed in connection with FIG. 12.

The response signal processor 2222 can be configured to process theresponse signal sensed from the eye 102 of the subject 104 by theresponse signal sensor to determine a measurement of oxygenation, bloodglucose, heart rate, glycosylated hemoglobin, temperature, bodytemperature, blood flow, or a substance in the eye of the subject fromthe response signal, for example, as discussed herein above.

In an embodiment, interrogation signal control circuitry 2520 can beconfigured to drive production of a pulsed interrogation signal by theinterrogation signal source. Signal processing circuitry may then beconfigured to gate detection of the response signal relative to thepulsed interrogation signal. Signal processing circuitry can beconfigured to combine multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal. For example, signal processing circuitry can be configured tocombine the multiple response signals by summing or averaging themultiple response signals, or by determining a moving average orweighted sum of the multiple response signals. Such an approach isillustrated in and described in connection with FIG. 6, for example.

The system can include interrogation signal control circuitry 2520configured to drive production of a first interrogation signal having afirst optical wavelength and production of a second interrogation signalhaving a second optical wavelength. Signal processing circuitry isconfigured to process a first response signal sensed from the eye of thesubject in response to the first interrogation signal and a secondresponse signal sensed from the eye of the subject in response to thesecond interrogation signal by comparing the first and second responsesignals in order to determine the physiological parameter, as describedin connection with FIG. 7. Signal processing circuitry 2502 can beconfigured to drive production of the first interrogation signalsimultaneously or sequentially with respect to the second interrogationsignal.

In an embodiment, the system includes an output structure 810 adapted tooutput a signal relating to the determined physiological parameter.Output structure 810 can be, for example, a data transmission structure,a data storage structure, a display, an audio output, or a visualoutput, as discussed in connection with FIG. 8. The system may include adisplay adapted to display information relating to the determinedphysiological parameter.

FIG. 26 depicts a system 2600 that includes a housing 1302; aninterrogation signal source 2202 housed in the housing 1302 and adaptedfor delivering an interrogation signal to an eye of a subject, theinterrogation signal source 2202 including at least one light source andat least one optical system; a response signal sensor 2206 housed withinthe housing 1302 and adapted for sensing a response signal produced bythe eye of the subject responsive to the interrogation signal, theresponse signal containing information regarding a physiologicalparameter of the subject; an input structure 2602 adapted for receivingan input signal; at least one actuator 2604 configured to adjust atleast one of the interrogation signal source 2202 or the response signalsensor 2206 based at least in part upon the input signal to bring atleast one of the interrogation signal source 2292 or the response signalsensor 2206 into alignment with the eye of the subject; an outputstructure 1320 adapted for transmitting an output signal 1322; andmounting means 1324 adapted for mounting the housing 1302 with respectto a display in such a manner that the interrogation signal source 2202and response signal sensor 2206 are alignable with the eye of thesubject during normal use of the display by the subject. Interrogationsignal source 2202 and response signal sensor 2206 are described hereinabove in connection with FIG. 22. Output structure 1320 is as describedin connection with FIG. 13. Various examples of mounting means 1324 aredescribed herein above, in connection with FIG. 13. In an embodiment,system 2600 includes a gaze signal sensor 2210 adapted for receiving agaze signal containing information indicative of a gaze direction of aneye of the subject.

In an embodiment, system 2600 includes signal processing circuitry 2220adapted for determining a target position for the at least one of theinterrogation signal source and the response signal sensor and forproviding an input signal indicative of the target position to the inputstructure.

System 2600 may also include at least one gaze tracking stimulus source150, as described herein above, adapted to deliver a gaze trackingstimulus to at least an eye of a subject, wherein the gaze signal isproduced in response to the gaze tracking stimulus. For example, gazetracking stimulus source can include an infra-red source, in which casegaze signal sensor may include an infra-red sensor, or a near infra-redsource, which may be used in combination with a gaze signal sensor thatincludes a near infra-red sensor. Gaze tracking stimulus source mayinclude a plurality of light sources. In an embodiment gaze signalsensor and the response signal sensor are the same sensor. In anotherembodiment, gaze signal sensor and the response signal sensor aredifferent sensors. In an embodiment, 2600 system includes signalprocessing circuitry 2220 adapted for determining at least oneinstruction for controlling actuator 2604.

In one aspect, mounting means 1324 can be adapted for mounting thehousing 1302 with respect to the display such that during normal use ofthe display by the subject, the interrogation signal source 2202 andresponse signal sensor 2206 are positioned within the visual field of atleast one eye of the subject. In one aspect, the mounting means 1324 isadapted for mounting the housing 1302 with respect to the display suchthat the interrogation signal source 2202 and response signal sensor2206 are oriented in substantially the same direction as the displaysurface of the display.

Response signal sensor 2206 may be adapted to sense a response signalfrom an interior of the eye of the subject responsive to theinterrogation signal, e.g., from a lens, an aqueous humor, a vitreoushumor, or a retina of the eye of the subject. Gaze signal sensor 2210may include an infrared camera, or a CCD camera. Gaze signal sensor 2210can include an optical sensor or an optical sensor array, which mayinclude, for example, a camera or a plurality of gaze signal sensors.

As discussed above, various combinations of interrogation signal source2202 and response signal sensor 2206 can be selected for detectingparticular analytes. For example, in an embodiment, interrogation signalsource 2202 includes a broad spectrum light source, and response signalsensor 2206 includes a spectrometer based on a CCD array. In anotherembodiment, interrogation signal source 2202 includes a near-infraredlight source and the response signal sensor 2206 includes anear-infrared camera. In another embodiment, interrogation signal source2202 includes a tunable laser source and wherein the response signalsensor 2206 includes a Raman spectrometer based on a CCD camera. Othercombinations include an interrogation signal source 2202 that includes amid-infrared light source and response signal sensor 2206 that includesa mid-infrared detector; and an interrogation signal source 2202 thatincludes a tunable laser source and response signal sensor 2206 thatincludes a broad spectrum pyroelectric detector.

In an embodiment, interrogation signal source 2202 is adapted to producelight having a first polarization, wherein the response signal sensor2206 is adapted to detect light having a second polarization, andwherein the first polarization and the second polarization are the same.In an embodiment, the interrogation signal source 2202 is adapted toproduce light having a first polarization, wherein the response signalsensor 2206 is adapted to detect light having a second polarization, andwherein the first polarization and the second polarization aredifferent.

The response signal may be indicative of a feature of the vasculature ofthe eye of the subject or a biometric identification of the subject. Thephysiological parameter can be, for example, a measurement ofoxygenation, blood glucose, heart rate, or glycosylated hemoglobin. Thephysiological parameter can be a temperature, e.g. a body temperature, ameasurement of blood flow, or a measurement of a substance in the eye ofthe subject.

In one aspect, the interrogation signal source 2202 is adapted todeliver a pulsed interrogation signal, as discussed herein above. Inconnection therewith, the response signal sensor 2206 can be configuredto gate detection of the response signal relative to the pulsedinterrogation signal.

In an embodiment, system 2600 includes signal processing circuitry 2220adapted to process the response signal. For example, the interrogationsignal source 2202 may be adapted to deliver a pulsed interrogationsignal, and the signal processing circuitry 2229 may be configured togate detection of the response signal relative to the pulsedinterrogation signal. In one aspect, signal processing circuitry 2220 isconfigured to combine multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal. Multiple response signals can be combined, e.g., by summing oraveraging the multiple response signals, or by determining a movingaverage or weighted sum of the multiple response signals.

In one aspect the interrogation signal source 2202 is adapted to deliveran interrogation signal containing multiple wavelengths of light. System2600 can include at least a first response signal sensor configured tosense a first response signal produced by the eye of the subjectresponsive to a first wavelength component of the interrogation signal,and a second response signal sensor configured to sense a secondresponse signal produced by the eye of the subject responsive to asecond wavelength component of the interrogation signal, as describedherein above, e.g. in connection with FIG. 7.

In an aspect, system 2600 includes at least a first interrogation signalsource 2202 configured to deliver a first interrogation signal having afirst optical wavelength and at least a second interrogation signalsource (not shown) configured to deliver a second interrogation signalhaving a second optical wavelength, as discussed in connection with FIG.7. Signal processing circuitry 2220 can be configured to process a firstresponse signal sensed from the eye of the subject in response to thefirst interrogation signal and a second response signal sensed from theeye of the subject in response to the second interrogation signal bycomparing the first and second response signals to determine thephysiological parameter. System 2600 can be configured to deliver thefirst interrogation signal simultaneously with respect to the secondinterrogation signal, or sequentially with respect to the secondinterrogation signal.

In some embodiments, interrogation signal source and the response signalsensor are co-aligned. In other embodiments, interrogation signal sourceand the response signal sensor can be separately aligned and located.

Output structure 1320 can include one or more of various structures,e.g. a data transmission structure, serial port, parallel port,electromagnetic transmission means, optical transmission means, audiooutput, or visual output. Output structure 1320 can be adapted totransmit an output signal to the display (e.g. display 1354), or to adata processing device 1352, for example. In an embodiment, the displayis controlled by the data processing device 1352. Display 1354 can beconfigured to display information relating to the determinedphysiological parameter. Display 1354 can be, for example, a videomonitor, computer display, video game display, telephone display,terminal of a data processing device, or other display as known to thosehaving skill in the relevant art. The display can be incorporated in awearable item (e.g., as described herein above), an article offurniture, an article of medical or health-care related equipment, anarticle of exercise equipment, or a vehicle. Examples of such displaysare described in greater detail herein above.

In an embodiment, system 2600 also includes a rangefinder 2240 adaptedfor determining the distance between the eye of the subject and theinterrogation signal source; and an autofocus system 2242 for focusingthe interrogation signal source responsive to the determined distance.In an embodiment, system 2600 includes a rangefinder 2240 adapted fordetermining the distance between the eye of the subject and the responsesignal sensor; and an autofocus system 2242 for focusing the responsesignal sensor responsive to the determined distance. Rangefinder 2240and autofocus system 2242 are discussed in greater detail in connectionwith FIG. 22.

In one aspect, actuator 2604 is configured to adjust the interrogationsignal source 2202 by adjusting the position of at least a portion ofthe interrogation signal source. Interrogation signal source can atleast one optical component, and the at least one actuator can beconfigured to adjust the interrogation signal source by adjusting atleast one optical component of the interrogation signal source.

In one aspect, actuator 2604 can be configured to adjust the responsesignal sensor 2206 by adjusting the position of at least a portion ofthe response signal sensor. Response signal sensor 2206 can include atleast one optical component, and the at least one actuator 2604 can beconfigured to adjust the response signal sensor by adjusting at leastone optical component of the response signal sensor. The interrogationsignal source 2202 and the response signal sensor 2206 can beco-aligned, or alternatively, the interrogation signal source and theresponse signal sensor can be separately aligned and located.

In an embodiment, the at least one actuator 2604 is configured to scanthe at least one of the interrogation signal source 2202 or the responsesignal sensor 2206 through a region in which the eye of the subject islocated such that the least one of the interrogation signal source andthe response signal sensor will be brought into alignment with the eyeof the subject at at least one position within the scanned region.

System 2600 can include data capture circuitry 2250 configured tocapture a response signal from the eye of the subject in connection withdetermination by the signal processing circuitry that the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor.

System 2600 may also include electrical circuitry 2320 configured tocause a visual stimulus to be displayed on the display to attract thegaze of the subject. The electrical circuitry 2320 can include at leastone of hardware, software, or firmware, and may be configured to causethe visual stimulus to be displayed at a location on the display suchthat when the gaze of the subject is directed toward the visual stimulusthe eye of the subject will be brought into alignment with respect tothe at least one of the interrogation signal source and the responsesignal sensor. Electrical circuitry 2320 can be configured to cause avisual stimulus to be displayed on the display that differs from avisual background. For example, electrical circuitry can be configuredto cause a visual stimulus to be displayed on the display that includesa different light intensity, different optical wavelength, differenttemporal pattern of light intensity, different temporal pattern ofoptical wavelength, different spatial pattern of light intensity, ordifferent spatial pattern of optical wavelength relative to a visualbackground. Electrical circuitry 2320 can be configured to cause avisual stimulus to be displayed on the display that includes an image, amoving image, or text.

FIG. 27 is a flow diagram of a method 2700 of measuring information froman eye of a subject, including; delivering an interrogation signal tothe eye of the subject with an interrogation signal source 2702;detecting a response signal from the eye of the subject with a responsesignal sensor 2704; receiving a signal indicative of the gaze directionof the eye of the subject from a gaze signal sensor 2706; determiningwhether the eye of the subject is in alignment with respect to at leastone of the interrogation signal source and the response signal sensor2708; if the eye of the subject is not in alignment with respect to theat least one of the interrogation signal source and the response signalsensor, actuating at least one actuator configured to adjust at leastone of the interrogation signal source and the response signal sensorbased at least in part upon the signal from the gaze signal sensor tobring at least one of the interrogation signal source and the responsesignal sensor into alignment with the eye of the subject 2710;determining a physiological parameter of the subject from the responsesignal detected from the eye of the subject when the eye of the subjectis in alignment with respect to the at least one of the interrogationsignal source and the response signal sensor 2712; and causing a signalindicative of the physiological parameter to be transmitted to anexternal device 2714.

As discussed elsewhere herein, various physiological parameters can bemeasured. In some method embodiments, the physiological parameter is ameasurement of a substance in the blood of the subject, as indicated at2716, and in some embodiments, the physiological parameter is ameasurement of a substance in an aqueous humor of the subject, asindicated at 2718. The physiological parameter can be a measurement ofoxygen 2720, glucose 2722, a salt 2724, a protein 2726, a lipid 2728, agas 2730 (e.g. oxygen), a hormone 2732, a drug 2734. The physiologicalparameter can be a pulse rate 2736, a blood flow 2738, or a temperature2740.

As shown in FIG. 28, a method 2800 is an expansion of the method shownin FIG. 27, which includes include determining the physiologicalparameter of the subject from the response signal detected from the eyeof the subject at one or more set times 2802, determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at a set time interval 2804, or determiningthe physiological parameter of the subject from the response signaldetected from the eye of the subject according to a programmed schedule2806. For example, the programmed schedule can be personalized for thesubject 2808, selected from among at least two pre-programmed schedulesbased upon at least one attribute of the subject 2810, or selected fromamong at least two pre-programmed schedules based upon the physiologicalparameter 2812.

A shown in FIG. 29, a method 2900 also includes reporting informationregarding the physiological parameter to an interested party 2902. Forexample, the interested party may include one or more of the subject, amedical service provider, a family member, a legal guardian or a legalrepresentative 2904. Method 2900 may include comparing the physiologicalparameter determined from the response signal to a previous measurementof the physiological parameter to determine a physiological trend 2906,and reporting information regarding the physiological trend to aninterested party 2908, e.g. one or more of the subject, a medicalservice provider, a family member, a legal guardian or a legalrepresentative 2910. In an aspect, method 2900 may include utilizing thephysiological parameter determined from the response signal to assessvarious states of the subject, e.g. an emotional state of the subject2912, or alertness of the subject 2914. The physiological parameterdetermined from the response signal can be used in a medical orhealth-related application 2916, or in a business or securityapplication 2918.

FIG. 30 depicts a method 3000 which includes steps 2702-2714 as depictedin FIG. 27. Method 3000 also includes presenting an input to the subject3002 and utilizing the physiological parameter determined from theresponse signal to determine a response of the subject to the input3004. The input may include, for example, information 3006 (e.g.advertising information 3008, marketing research information 3010, printinformation 3012, or video information 3014), an auditory stimulus 3016,a visual stimulus 3018, a tactile stimulus 3020, an olfactory stimulus3022, a gustatory stimulus 3024, a thermal stimulus 3026, a neuralstimulus 3028, or a drug, a pharmaceutical, a nutraceutical, or anutrient 3030.

FIG. 31 depicts a method 3100 which includes steps 2702-2714 asdescribed in connection with FIG. 27. In addition method 3100 includesdelivering an interrogation signal to the eye of the subject with aninterrogation signal source and detecting a response signal from the eyeof the subject with a response signal sensor can be performedunobtrusively, as indicated at 3102, or, in some applications, withoutdetection by the subject, as indicated at 3104. As discussed hereinabove, the method may include receiving an input indicative of aninstruction from the subject or representative of the subject forinformation to be measured 3106, receiving an input indicative ofauthorization from the subject or representative of the subject forinformation to be measured 3108, or receiving an input indicative ofinformed consent from the subject or representative of the subject forinformation to be measured 3110.

In an aspect, a method 3200 depicted in FIG. 32 includes steps 2702-2714as shown in FIG. 27, and also includes transmitting at least one ofinformation regarding the subject, information regarding the system usedfor determining the physiological parameter, or information regardingthe physiological parameter to a data processing system 3202. In anaspect, a method includes receiving at least one of informationregarding the subject, information regarding the system used fordetermining the physiological parameter, or information regarding thephysiological parameter from a data processing system 3204. A method mayalso include sharing at least one of information regarding the subject,information regarding the system used for determining the physiologicalparameter, or information regarding the physiological parameter betweentwo or more data processing systems 3206.

In an aspect, the method includes determining the identity of thesubject 3208, e.g. through the use of facial recognition 3210 or retinalrecognition 3212, or by comparing login information entered by thesubject with login information in a registry 3214. As discussed hereinabove in connection with FIG. 20, in an aspect, delivering theinterrogation signal to the eye of the subject with the interrogationsignal source can be done only when the identity of the subject meets aselection criterion, e.g., matching an identity of an approved subject.

FIG. 33 depicts an article of manufacture 3300 as generally described inconnection with FIG. 21, the article of manufacture including one ormore non-transitory machine-readable data storage media 3302 bearing oneor more instructions 3304 for carrying out a method as shown in FIG. 27,including delivering an interrogation signal to the eye of the subjectwith an interrogation signal source; detecting a response signal fromthe eye of the subject with a response signal sensor; receiving a signalindicative of the gaze direction of the eye of the subject from a gazesignal sensor; determining whether the eye of the subject is inalignment with respect to at least one of the interrogation signalsource and the response signal sensor; if the eye of the subject is notin alignment with respect to the at least one of the interrogationsignal source and the response signal sensor, actuating at least oneactuator configured to adjust at least one of the interrogation signalsource and the response signal sensor based at least in part upon thesignal from the gaze signal sensor to bring at least one of theinterrogation signal source and the response signal sensor intoalignment with the eye of the subject; determining a physiologicalparameter of the subject from the response signal detected from the eyeof the subject when the eye of the subject is in alignment with respectto the at least one of the interrogation signal source and the responsesignal sensor; and causing a signal indicative of the physiologicalparameter to be transmitted to an external device, as shown in FIG. 27.As discussed above, the physiological parameter can be a measurement ofa substance in the blood of the subject (e.g., oxygen, glucose, a salt,a protein, or a lipid), a measurement of a substance in an aqueous humorof the subject (e.g., oxygen, glucose, a salt, a protein, or a lipid, ahormone, a drug), or pulse rate.), or other parameters as discussedelsewhere herein.

The data storage media 3302 can bear one or more instructions 3304 forperforming a method as shown in FIG. 28, including determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at one or more set times, determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at a set time interval, or determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject according to a programmed schedule. The datastorage media can bear one or more instructions for personalizing theprogrammed schedule for the subject, for example by selecting theprogrammed schedule from among at least two pre-programmed schedulesbased upon at least one attribute of the subject, or selecting theprogrammed schedule from among at least two pre-programmed schedulesbased upon the physiological parameter.

In an embodiment, the data storage media 3302 can bear one or moreinstructions for reporting information regarding the physiologicalparameter to an interested party, for example, one or more of thesubject, a medical service provider, a family member, a legal guardianor a legal representative. In an embodiment, the data storage media canbear one or more instructions for comparing the physiological parameterdetermined from the response signal to a previous measurement of thephysiological parameter to determine a physiological trend. In addition,the data storage media can bear one or more instructions for reportinginformation regarding the physiological trend to an interested party,for example one or more of the subject, a medical service provider, afamily member, a legal guardian or a legal representative.

The data storage media 3302 can bear instructions for utilizing thephysiological parameter determined from the response signal to assess anemotional state of the subject, or assess the alertness of the subject.In an embodiment, the data storage media can bear one or moreinstructions for utilizing the physiological parameter determined fromthe response signal in a medical or health-related application.Alternatively, or in addition, the data storage media can bear one ormore instructions for utilizing the physiological parameter determinedfrom the response signal in a business or security application.

The data storage media 3302 can bear one or more instructions forperforming a method as shown in FIG. 30, including one or moreinstructions for presenting an input to the subject; and utilizing thephysiological parameter determined from the response signal to determinea response of the subject to the input. For example, the input caninclude information (e.g., advertising information, marketing researchinformation, print information, or video information), an auditorystimulus, a visual stimulus, a tactile stimulus, an olfactory stimulus,a gustatory stimulus, a thermal stimulus, a neural stimulus, a drug, apharmaceutical, a nutraceutical, or a nutrient.

The data storage media 3302 can bear one or more instructions forperforming a method as shown in FIG. 31, including one more instructionsfor delivering an interrogation signal to the eye of the subject with aninterrogation signal source and detecting a response signal from the eyeof the subject with a response signal sensor unobtrusively, or one ormore instructions for: delivering an interrogation signal to the eye ofthe subject with an interrogation signal source and detecting a responsesignal from the eye of the subject with a response signal sensor areperformed without detection by the subject.

In addition, data storage media 3302 can bear instructions for receivingan input indicative of an instruction from the subject or representativeof the subject for information to be measured, receiving an inputindicative of authorization from the subject or representative of thesubject for information to be measured, or receiving an input indicativeof informed consent from the subject or representative of the subjectfor information to be measured, as discussed above.

In an embodiment, the data storage media 3302 can bear one or moreinstructions for performing a method as shown in FIG. 32, includingtransmitting at least one of information regarding the subject,information regarding the system used for determining the physiologicalparameter, or information regarding the physiological parameter to adata processing system. The data storage media can bear one or moreinstructions for receiving at least one of information regarding thesubject, information regarding the system used for determining thephysiological parameter, or information regarding the physiologicalparameter from a data processing system. In an embodiment, the datastorage media 3302 bear one or more instructions for sharing at leastone of information regarding the subject, information regarding thesystem used for determining the physiological parameter, or informationregarding the physiological parameter between two of more dataprocessing systems. In an embodiment, data storage media 3302 bear oneor more instructions for determining the identity of the subject, e.g.through the use of facial recognition or retinal recognition, or bycomparing login information entered by the subject with logininformation in a registry.

FIG. 34 is a schematic diagram of a system 3400 for sensing informationfrom an eye 102 of a subject 104, including an interrogation signalsource 110 for delivering an interrogation signal 112 to an eye 102 of asubject 104; a response signal sensor 114 for sensing a response signal116 produced by the eye 102 of the subject 104 responsive to theinterrogation signal 112; and signal processing circuitry 3402including: a response signal processor 3404 configured to process aresponse signal sensed 116 from the eye 102 of the subject 104 todetermine a physiological parameter 126 from the response signal 116;and a scheduling controller 3406 configured to direct collection ofsamples of the physiological parameter according to a schedule 3407.

In one aspect, scheduling controller 3406 can be configured to directcollection of a predetermined number of samples 3408 of thephysiological parameter during a sampling period. In one aspect,scheduling controller 3406 can be configured to direct collection ofsamples with at least a minimum sampling interval between samples.Scheduling controller 3406 can be configured to modify the procedure forcollecting a sample of the physiological parameter if a predeterminednumber of samples meeting an acceptance criterion 3410 has not beencollected within a predetermined portion of the sampling period. Forexample, modifying the procedure for collecting a sample of thephysiological parameter can include modifying the acceptance criterion3410, which may be, for example, a signal-to-noise ratio criterion 3412or a sampling interval criterion 3414. For example, if not enoughsamples meeting an acceptance signal-to-noise ratio acceptance criterionhave been met, a lower signal-to-noise ratio criterion ratio may be set,so that a larger number of samples meet the acceptance criterion. Itwill be appreciated that in some embodiments of methods describedherein, sampling of data is performed continuously or substantiallycontinuously, while collection of samples includes retaining a subset ofthe sampled data, based upon a schedule and according to otheracceptance criterion, as discussed herein above, for further analysis.For example, sampled data may be retained temporarily in a buffer orother location, whereas collected samples may be stored in a separatememory location or transmitted to a remote location for longer termstorage and/or analysis. In other embodiments, data sampling isperformed only when certain criterion are met (e.g. alignment of the eyeof the subjects with interrogation signal source and/or response signalsensor, schedule criterion, acceptance criterion, etc.) and collectingsamples is consequently substantially the same as sampling data.

As shown in FIG. 34, system 3400 can include a gaze signal sensor 106adapted for receiving a gaze signal 108 containing informationindicative of a gaze direction of an eye 102 of the subject 104; andwherein the signal processing circuitry 3402 includes: a gaze signalprocessor 120 configured to determine the gaze direction of the eye ofthe subject based upon the gaze signal; and an alignment detector 122configured to determine whether the eye 102 of the subject 104 is inalignment with respect to at least one of the interrogation signalsource 110 or the response signal sensor 114; wherein the responsesignal processor is configured to process the response signal 116 sensedfrom the eye 102 of the subject 104 when the eye of the subject is inalignment with respect to the at least one of the interrogation signalsource and the response signal sensor to determine the physiologicalparameter 126 from the response signal.

Signal processing circuitry 3402 may be configured to cause thealignment of the eye 102 of the subject 104 with respect to the at leastone of the interrogation signal source and the response signal sensor ifa predetermined number of samples meeting an acceptance criterion 3410has not been collected within a predetermined portion of the samplingperiod. Alignment of eye 102 with interrogation signal source 110 and/orresponse signal sensor 114 can be achieved by causing the subject 104 todirect his or her gaze toward interrogation signal source 110 and/orresponse signal sensor 114, and/or by directing interrogation signalsource 110 and/or response signal sensor 114 toward eye 102.

System 3400 can include at least one actuator (134 or 140) configured tomove at least one of the interrogation signal source 110 or the responsesignal sensor 114, respectively; wherein the signal processing circuitry3402 is configured to cause the alignment of the eye of the subject withrespect to the at least one of the interrogation signal source 110 orthe response signal sensor 114 by directing the actuator (134 or 140) tomove at least one of the interrogation signal source 110 or the responsesignal sensor 114 into alignment with the eye 102 of the subject 104.

In an embodiment, system 3400 also includes a gaze attractor 3416adapted to attract the gaze of the subject 104 to thereby cause the eye102 of the subject 104 to move into alignment with at least one of theinterrogation signal source 110 or the response signal sensor 114;wherein the signal processing circuitry 3402 is configured to activatethe gaze attractor 3416 to cause the alignment of the eye of the subjectwith respect to the at least one of the interrogation signal source 110or the response signal sensor 114 if a predetermined number of samplesmeeting an acceptance criterion has not been collected within apredetermined portion of the sampling period. Gaze attractor may be 3416any structure capable of attracting the gaze of the subject, byattracting the attention of the subject such that the subject directshis or her gaze toward the gaze attractor. For example, gaze attractormay be capable of delivering a visual stimulus 3418, an audio stimulus3420, or both, simultaneously or in sequence, as discussed in connectionwith FIG. 23.

Response signal sensor 114 can be adapted to sense a response signalfrom an interior of the eye of the subject responsive to theinterrogation signal, e.g. from a lens, aqueous humor, vitreous humor,or a retina of the eye of the subject.

In some embodiments, gaze signal sensor 106 and the response signalsensor 114 may be different sensors, as depicted in FIG. 34, or, asdepicted in FIG. 3, gaze signal sensor 106 and the response signalsensor 114 are may be the same sensor. Gaze signal sensor can be aninfrared camera or a CCD camera, as discussed herein above.

Various combinations of interrogation signal source 110 and responsesignal sensor 114 can be used, depending on the physiological parameterto be sensed, as discussed herein above. For example, in one embodiment,interrogation signal source 110 includes a broad spectrum light sourceand response signal sensor 114 includes a spectrometer based on a CCDarray. In another embodiment, wherein the interrogation signal source110 includes a near-infrared light source and the response signal sensor114 includes a near-infrared camera. Other such combinations includeinterrogation signal source 110 includes a tunable laser source and theresponse signal sensor 114 includes a Raman spectrometer based on a CCDcamera, interrogation signal source 110 includes a mid-infrared lightsource and the response signal sensor 114 includes a mid-infrareddetector, and interrogation signal source 110 includes a tunable lasersource and the response signal sensor 114 includes a broad spectrumpyroelectric detector.

Response signal may be indicative of a feature of the vasculature of theeye of the subject or a biometric identification of the subject.

In an embodiment, system also includes at least one gaze trackingstimulus 150 source adapted to deliver a gaze tracking stimulus 152 toat least an eye of a subject, wherein the gaze signal 108 is produced inresponse to the gaze tracking stimulus 152. Gaze tracking stimulussource 150 may include, for example, an infra-red source, which may beused in combination with a gaze signal sensor 106 that includes aninfra-red sensor. Gaze tracking stimulus source may include a nearinfra-red source, which may be used in combination with a gaze signalsensor 106 that includes a near infra-red sensor. Gaze tracking stimulussource 150 may include one or a plurality of light sources. Gaze signalsensor 106 may include an optical sensor, an optical sensor array, or acamera. System may include a plurality of gaze signal sensors.

In an embodiment, the interrogation signal source 110 is adapted toproduce light having a first polarization, and the response signalsensor 114 is adapted to detect light having a second polarization, asdiscussed herein above in connection with FIG. 12. The firstpolarization and the second polarization may be the same, or different.

As in other embodiments discussed herein, various physiologicalparameters can be measured. The physiological parameter may be ameasurement of oxygenation, measurement of blood glucose, a heart rate,a measurement of glycosylated hemoglobin, a temperature, e.g., a bodytemperature, a measurement of blood flow, or a measurement of asubstance in the eye of the subject, for example.

As discussed generally in connection with FIG. 6, interrogation signalsource 110 may be adapted to deliver a pulsed interrogation signal. Inconnection therewith, at least one of the response signal sensor 114 andthe signal processing circuitry 3402 may be configured to gate detectionof the response signal relative to the pulsed interrogation signal.Signal processing circuitry 3402 may be configured to combine multipleresponse signals produced by the eye of the subject in response tomultiple pulses of the pulsed interrogation signal. For example, signalprocessing circuitry may be configured to combine the multiple responsesignals by summing or averaging the multiple response signals, or bydetermining a moving average or weighted sum of the multiple responsesignals.

In an embodiment, interrogation signal source 110 is adapted to deliveran interrogation signal containing multiple wavelengths of light. Inconnection therewith system 3400 may include includes at least a firstresponse signal sensor configured to sense a first response signalproduced by the eye of the subject responsive to a first wavelengthcomponent of the interrogation signal, and a second response signalsensor (not shown) configured to sense a second response signal producedby the eye of the subject responsive to a second wavelength component ofthe interrogation signal. See, e.g. FIG. 7.

In an embodiment, system 3400 includes at least a first interrogationsignal source configured to deliver a first interrogation signal havinga first optical wavelength and at least a second interrogation signalsource configured to deliver a second interrogation signal having asecond optical wavelength. Signal processing circuitry may be configuredto process a first response signal sensed from the eye of the subject inresponse to the first interrogation signal and a second response signalsensed from the eye of the subject in response to the secondinterrogation signal by comparing the first and second response signalsto determine the physiological parameter. See, e.g. FIG. 7. System 3400may be configured to deliver the first interrogation signalsimultaneously with respect to the second interrogation signal, orsequentially with respect to the second interrogation signal.

Interrogation signal source 110 and response signal sensor 114 can beco-aligned, or separately aligned and located.

In an embodiment, system 3400 includes an output structure 810 adaptedto output a signal relating to the determined physiological parameter.The output structure can be a data transmission structure, a datastorage structure, a display, an audio output, or a visual output, forexample, as discussed in connection with FIG. 8. In one aspect, system3400 can include a display adapted to display information relating tothe determined physiological parameter. The display can be, for example,a video monitor, a computer display, a video game display, a telephonedisplay, or a data processing device. The display may be incorporated ina wearable item, an article of furniture, an article of medical orhealth-care related equipment, an article of exercise equipment, or avehicle. Examples of such displays are described in greater detailherein above.

FIG. 35 depicts a system 3500 for controlling the sensing of informationfrom an eye 102 of a subject 104, including signal processing circuitry3502 including: a response signal input 3504 adapted to receive aresponse signal 3506 sensed from the eye 102 of the subject 104 by aresponse signal sensor 114 responsive to delivery of an interrogationsignal 112 to the eye 102 of the subject 104; and a response signalprocessor 3404 configured to process the response signal sensed from theeye of the subject by the response signal sensor to determine aphysiological parameter 126 from the response signal; and a schedulingcontroller 3406 configured to direct collection of samples 3408 of thephysiological parameter according to a schedule 3407.

System 3500 may include a gaze signal input 3508 adapted to receive agaze signal 3510 containing information indicative of a gaze directionof the eye of the subject sensed from at least an eye of the subject;and a gaze signal processor 120 configured to determine the gazedirection 3512 of the eye 102 of the subject 104 based upon the gazesignal 3510; and an alignment detector 122 configured to determinewhether the eye of the subject is in alignment with respect to at leastone of the interrogation signal source 110 or the response signal sensor114 based at least in part upon the gaze direction 3512.

System may 3500 include gaze tracking stimulus control circuitry 3514configured to drive production of gaze tracking stimulus 152 by a gazetracking stimulus source 1022, wherein the gaze signal 108 is producedresponsive to the gaze tracking stimulus 1022. In an embodiment, gazetracking stimulus control circuitry 3514 is configured to driveproduction of a gaze tracking stimulus by a plurality of gaze trackingstimulus sources (not shown). Gaze signal input 3508 and the responsesignal input 3504 can be the same input (e.g. if same sensor is used asthe gaze signal sensor and the response signal sensor). Alternatively,the gaze signal input 3508 and the response signal input 3504 can beseparate inputs, e.g. gaze signal sensor and response signal sensor areseparate sensors. The gaze signal input 3508 may be configured toreceive various types of signals. In an embodiment, gaze signal input3508 is adapted to receive a signal from a camera. In an embodiment,signal processing circuitry includes a plurality of gaze signal inputs(not shown in FIG. 35, but generally as depicted in FIG. 12) adapted toreceive a plurality of gaze signals containing information indicative ofa gaze direction of the eye of the subject sensed from at least an eyeof the subject. System 3500 may also include interrogation signalcontrol circuitry 3516 configured to drive production of interrogationsignal 112 by interrogation signal source 110.

Response signal processor 3404 may be adapted to process a responsesignal 3506 sensed from an interior of the eye of the subject responsiveto the interrogation signal, e.g. a response signal sensed from a lens,aqueous humor, vitreous humor, or retina of the eye of the subject.Response signal processor 3404 can be configured to process the responsesignal 3506 to determine a feature of the vasculature of the eye of thesubject or determine a biometric identification of the subject, asdescribed herein above. In an embodiment, response signal processor 3404is configured to process the response signal by determining a firstresponse signal at a first polarization, determining a second responsesignal at a second polarization, and comparing the response signaldetermined at the first polarization to the response signal determinedat the second polarization, wherein the first polarization and thesecond polarization are different, discussed above in connection withFIG. 12.

Response signal processor 3404 can be configured to process the responsesignal 3506 sensed from the eye of the subject by the response signalsensor 114 when the eye of the subject is in alignment with respect tothe at least one of the interrogation signal source and the responsesignal sensor to determine a measurement of a physiological parameterfrom the response signal, including, for example, oxygenation, bloodglucose, heart rate, glycosylated hemoglobin, temperature, bodytemperature, blood flow, or a substance in the eye of the subject fromthe response signal.

In an embodiment, interrogation signal control circuitry 3516 isconfigured to drive production of a pulsed interrogation signal by theinterrogation signal source, as discussed above in connection with FIG.6. Signal processing circuitry 3502 may be configured to gate detectionof the response signal relative to the pulsed interrogation signal. Inone aspect, signal processing circuitry 3502 is configured to combinemultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal, by summing oraveraging the multiple response signals, or by determining a movingaverage or weighted sum of the multiple response signals.

In an embodiment, system includes interrogation signal control circuitry3516 configured to drive production of a first interrogation signalhaving a first optical wavelength and production of a secondinterrogation signal having a second optical wavelength, as described inconnection with FIG. 7. Signal processing circuitry 3516 may beconfigured to process a first response signal sensed from the eye of thesubject in response to the first interrogation signal and a secondresponse signal sensed from the eye of the subject in response to thesecond interrogation signal by comparing the first and second responsesignals in order to determine the physiological parameter. Signalprocessing circuitry 3516 may be configured to drive production of thefirst interrogation signal simultaneously with respect to the secondinterrogation signal, or sequentially with respect to the secondinterrogation signal.

In an embodiment, scheduling controller 3406 is configured to directcollection of a predetermined number of samples of the physiologicalparameter during a sampling period. In an embodiment, schedulingcontroller 3406 is configured to direct collection of samples with atleast a minimum sampling interval between samples. In an aspect,scheduling controller 3406 is configured to modify the procedure forcollecting a sample of the physiological parameter if a predeterminednumber of samples meeting an acceptance criterion 3410 has not beencollected within a predetermined portion of the sampling period.Modifying the procedure for collecting a sample of the physiologicalparameter may be done, for example by modifying the acceptance criterion3410. Acceptance criterion may include one or more of signal-to-noiseratio criterion 3412 and sampling interval criterion 3414.

In an embodiment, signal processing circuitry 3502 is configured tocause the alignment of the eye of the subject with respect to the atleast one of the interrogation signal source and the response signalsensor if a predetermined number of samples meeting an acceptancecriterion has not been collected within a predetermined portion of thesampling period. System 3500 may also include at least one actuator (134or 140) configured to move at least one of the interrogation signalsource 110 or the response signal sensor 114; wherein the signalprocessing circuitry 3502 is configured to cause the alignment of theeye of the subject with respect to the at least one of the interrogationsignal 110 source or the response signal sensor 114 by directing anactuator 134 or 140, respectively, to move at least one of theinterrogation signal 110 source or the response signal sensor 114 intoalignment with the eye 102 of the subject 104. In an embodiment, signalprocessing circuitry 3502 may be configured to activate a gaze attractor3416 to cause the alignment of the eye of the subject with respect tothe at least one of the interrogation signal source and the responsesignal sensor if a predetermined number of samples meeting an acceptancecriterion has not been collected within a predetermined portion of thesampling period. The response signal 3506 may be indicative of a featureof the vasculature of the eye of the subject or a biometricidentification of the subject.

FIG. 36 depicts a system 3600 that includes a housing 3602; aninterrogation signal source 3604 housed in the housing 3602 and adaptedfor delivering an interrogation signal to an eye of a subject, theinterrogation signal source 3604 including at least one light source andat least one optical system; a response signal sensor 3606 housed withinthe housing 3602 and adapted for sensing a response signal produced bythe eye of the subject responsive to the interrogation signal, theresponse signal containing information regarding a physiologicalparameter of the subject; signal processing circuitry 3608 including: aresponse signal processor 3404 configured to process a response signalsensed from the eye of the subject to determine a physiologicalparameter from the response signal; and a scheduling controller 3406configured to direct collection of samples of the physiologicalparameter according to a schedule 3407; an output structure 810 adaptedfor transmitting an output signal; and mounting means 1324 adapted formounting the housing 3602 with respect to a display in such a mannerthat the interrogation signal source 3604 and response signal sensor3606 are alignable with the eye of the subject during normal use of thedisplay by the subject.

In one aspect, scheduling controller 3406 is configured to directcollection of a predetermined number of samples of the physiologicalparameter during a sampling period. In one aspect, scheduling controller3406 is configured to direct collection of samples with at least aminimum sampling interval between samples. Scheduling controller 3406may be configured to modify the procedure for collecting a sample of thephysiological parameter if a predetermined number of samples meeting anacceptance criterion 3410 has not been collected within a predeterminedportion of the sampling period, for example by modifying the acceptancecriterion. Acceptance criterion 3410 may include, for example, asignal-to-noise ratio criterion 3412 and/or a sampling intervalcriterion 3414.

In an embodiment, a system 3600 includes a gaze signal sensor 106adapted for receiving a gaze signal containing information indicative ofa gaze direction of an eye of the subject; and wherein the signalprocessing circuitry includes: a gaze signal processor 120 configured todetermine the gaze direction of the eye of the subject based upon thegaze signal; and an alignment detector 122 configured to determinewhether the eye of the subject is in alignment with respect to at leastone of the interrogation signal source 3604 or the response signalsensor 3606; wherein the response signal processor 3404 is configured toprocess the response signal sensed from the eye of the subject when theeye of the subject is in alignment with respect to the at least one ofthe interrogation signal source 3604 or the response signal sensor 3606to determine the physiological parameter from the response signal. Thephysiological parameter may be a measurement of oxygenation, bloodglucose, heart rate, glycosylated hemoglobin, temperature, bodytemperature, blood flow, or a substance in the eye of the subject, forexample.

System 3600 may also include at least one actuator 3610 configured tomove at least one of the interrogation signal source 3604 or theresponse signal sensor 3606; wherein the signal processing circuitry3608 is configured to cause the alignment of the eye of the subject withrespect to the at least one of the interrogation signal source 3604 orthe response signal sensor 3606 by directing the actuator 3610 to moveat least one of the interrogation signal source 3604 or the responsesignal sensor 3606 into alignment with the eye of the subject.

In an embodiment, system 3600 includes a gaze attractor 3416 adapted toattract the gaze of the subject to thereby cause the eye of the subjectto move into alignment with at least one of the interrogation signalsource and the response signal sensor; wherein the signal processingcircuitry 3608 is configured to activate the gaze attractor 3416 tocause the alignment of the eye of the subject with respect to the atleast one of the interrogation signal source 3604 or the response signalsensor 3606 if a predetermined number of samples meeting an acceptancecriterion has not been collected within a predetermined portion of thesampling period. As discussed above, response signal sensor 3606 may beadapted to sense a response signal from an interior of the eye of thesubject responsive to the interrogation signal, for example from a lens,aqueous humor, vitreous humor or retina of the eye of the subjectresponsive to the interrogation signal. Gaze signal sensor 106 and theresponse signal sensor 3606 may be the same sensor, or differentsensors, depending on the parameter to be sensed and preferred methodfor determining gaze direction. For example, gaze signal sensor caninclude an infrared camera or a CCD camera.

Various combinations of interrogation signal source 3604 and responsesignal sensor 3606 may be used, as discussed herein above. For example,in an embodiment, the interrogation signal source 3604 includes a broadspectrum light source and the response signal sensor 3606 includes aspectrometer based on a CCD array. Other combinations include aninterrogation signal source 3604 that includes a near-infrared lightsource and response signal sensor 3606 that includes a near-infraredcamera, an interrogation signal source 3604 that includes a tunablelaser source and response signal sensor 3606 that includes a Ramanspectrometer based on a CCD camera, an interrogation signal source 3604that includes a mid-infrared light source and response signal sensor3606 that includes a mid-infrared detector, and an interrogation signalsource 3604 that includes a tunable laser source and response signalsensor 3606 that includes a broad spectrum pyroelectric detector.

System 3600 may include at least one gaze tracking stimulus source 150adapted to deliver a gaze tracking stimulus to at least an eye of asubject, wherein the gaze signal is produced in response to the gazetracking stimulus. Gaze tracking stimulus source 150 may include, forexample, an infra-red source, while gaze signal sensor 106 includes aninfra-red sensor. Gaze tracking stimulus source 150 may include a nearinfra-red source, and gaze signal sensor 106 may include a nearinfra-red sensor. In some embodiment, gaze tracking stimulus source 150includes a plurality of light sources. Gaze signal sensor 106 caninclude an optical sensor, an optical sensor array, a camera, and/or aplurality of gaze signal sensors, for example.

In an embodiment, interrogation signal source 3604 is adapted to producelight having a first polarization, and response signal sensor 3606 isadapted to detect light having a second polarization, wherein the firstpolarization and the second polarization are the same. Alternatively,interrogation signal source 3604 may be adapted to produce light havinga first polarization, and the response signal sensor 3606 is adapted todetect light having a second polarization, wherein the firstpolarization and the second polarization are different.

In an embodiment, interrogation signal source 3604 is adapted to delivera pulsed interrogation signal, as described in connection with FIG. 6.In one aspect, at least one of response signal sensor 3606 and signalprocessing circuitry 3608 is configured to gate detection of theresponse signal relative to the pulsed interrogation signal. Signalprocessing circuitry 3608 may be configured to combine multiple responsesignals produced by the eye of the subject in response to multiplepulses of the pulsed interrogation signal, for example by summing oraveraging the multiple response signals, or by determining a movingaverage or weighted sum of the multiple response signals.

In an embodiment, a system 3600 includes an interrogation signal source3604 adapted to deliver an interrogation signal containing multiplewavelengths of light. As discussed generally elsewhere herein, system3600 may include at least a first response signal sensor configured tosense a first response signal produced by the eye of the subjectresponsive to a first wavelength component of the interrogation signal,and a second response signal sensor (not shown) configured to sense asecond response signal produced by the eye of the subject responsive toa second wavelength component of the interrogation signal. In anembodiment, a system includes a first interrogation signal sourceconfigured to deliver a first interrogation signal having a firstoptical wavelength and at least a second interrogation signal source(not shown) configured to deliver a second interrogation signal having asecond optical wavelength. Signal processing circuitry 3608 may beconfigured to process a first response signal sensed from the eye of thesubject in response to the first interrogation signal and a secondresponse signal sensed from the eye of the subject in response to thesecond interrogation signal by comparing the first and second responsesignals to determine the physiological parameter. The system may beconfigured to deliver the first interrogation signal simultaneously withrespect to the second interrogation signal, sequentially with respect tothe second interrogation signal. Interrogation signal source 3604 andthe response signal sensor 3606 may be co-aligned, or separately alignedand located.

In one aspect, mounting means 1324 is adapted for mounting the housing3602 with respect to the display such that during normal use of thedisplay by the subject, the interrogation signal source 3604 andresponse signal sensor 3606 are positioned within the visual field of atleast one eye of the subject. In one aspect, mounting means 1324 isadapted for mounting the housing 3602 with respect to the display suchthat the interrogation signal source 3604 and response signal sensor3606 are oriented in substantially the same direction as the displaysurface of the display.

Output structure 1320 may include a data transmission structure, whichmay be, for example, a serial port, a parallel port, an electromagnetictransmission means, an optical transmission means, an audio output or avisual output, as discussed herein above. Output structure 1320 may beadapted to transmit an output signal to display 1354, or data processingdevice 1352. In a related embodiment, the display 1354 is controlled bythe data processing device. Display 1354 may be configured to displayinformation relating to the determined physiological parameter, and maybe any of various types of displays, for example, a video monitor,computer display, video game display, telephone display, or terminal ofa data processing device. Display 1354 can be incorporated in a wearableitem, article of furniture, article of medical or health-care relatedequipment, article of exercise equipment, or vehicle. Examples of suchdisplays are described in greater detail herein above.

EXAMPLE 3 An Unobtrusive Eye Interrogation System Associated with aHospital TV to Measure Health Parameters on a Predetermined Schedule

FIG. 37 illustrates an eye interrogation system 3700 that is used tomeasure a patient's health parameters according to a schedule. Eyeinterrogation system 3700 is placed adjacent to a hospital patient'stelevision 3702 to measure health parameters according to apredetermined schedule. The eye interrogation system includes aninterrogation signal source 3704, a response signal sensor 3706 and asignal processing circuitry 3708 which are housed in the unit 3710 thatis mounted with respect to the patient's TV 3702. Eye interrogationsystem 3700 also includes a scheduling controller 3406 and a gazeattractor 3712 to engage the eyes of the patient 3714 to collect healthparameter data according to a schedule.

The eye interrogation system employs a mid-infrared wavelengthinterrogation signal source 3704 and response signal sensor 3706 tononinvasively identify bioanalytes and determine their concentration inthe eye. The system includes a gaze attractor 3712 to attract thepatients gaze to interrogation signal source 3704 and response signalsensor 3706. For example, gaze attractor 3712 may include a lightemitting diode (LED) which draws the patient's gaze to interrogationsignal source 3704 and response signal sensor 3706 when a bioanalytedetermination is scheduled. For example the LED may flash to attract thepatients' attention. A gaze tracking system 3720 is used to detect whenthe user looks at the LED gaze attractor 3712 and the interrogationsignal source and/or the response signal sensor. The gaze trackingsystem 3720 is comprised of an IR light source 3722 and an IR camera3724 which detects the reflection of IR light from the eyes of thepatient. Eye position, eye rotation, eye gaze position against screen,pupil diameter and eye vergence distance may be monitored. The gazetracking system 3720 includes software and circuitry to analyze the gazetracking data and to detect alignment of the patient's gaze with theinterrogation source and/or the interrogation detectors. Alignment ofthe patient's eyes with the interrogation sources and detectors triggersactivation of the interrogation source by the system controller.

Interrogation signal source 3704 interrogates the patient's eyes withmid-infrared light, which may be approximately 2.5 to 50.0 microns inwavelength. A range of mid-infrared wavelengths is sourced from tunableexternal cavity lasers which provide multiple wavelengths forspectroscopy of bioanalytes (e.g., the Uber Tuner™ Lasers available fromDaylight Solutions Inc., San Diego, Calif.; see the Product Sheet: “UberTuner™ Broad Tuning Pulsed Lasers” which is incorporated herein byreference). For example, tunable lasers emitting mid-infrared radiationat wavelengths between about 8 microns and about 11 microns may be usedto identify glucose which displays an absorption signature at thosewavelengths. Irradiation of the blood vessels in the sclera of the eyewith 8-11 micron wavelength light results in reflected spectra that maybe detected by mid-infrared detectors. For example a deuteratedtri-glycine sulfate pyroelectric detector may be used to detect thereflected mid-infrared radiation and determine the absorption pattern.Broad spectrum pyroelectric detectors to detect wavelengths betweenapproximately 700 nm and 28 microns are available from Newport Corp.,Irvine, Calif. (see the Specification Sheet: “MIR8025™ Modular IRFourier Spectrometers” which is incorporated herein by reference).Signal processors and associated software determine the radiationpattern and correlate the pattern with the known radiation signatures ina reference database. For example, an absorption pattern at wavelengthsbetween approximately 8 and 11 microns may be used to identify glucoseand to determine its concentration (see e.g. U.S. Pat. No. 6,958,039issued to Burd et al. on Oct. 25, 2005 which is incorporated herein byreference).

Eye interrogation system 3700 includes signal processing circuitry 3708to analyze bioanalyte concentrations, compare them to reference valuesor to values determined previously for the patient. For example, glucoseconcentration in conjunctiva blood vessels may be compared to correlatedglucose concentrations in the peripheral circulation and to a normalrange for glucose. Also the glucose concentrations determined accordingto a predetermined schedule may be compared. Blood glucoseconcentrations outside the normal range or trending rapidly tohyperglycemia are reported electronically to computer terminals of theresponsible health caregivers.

Eye interrogation system 3700 may be used to monitor a patient's bloodconcentration of a pharmaceutical such as warfarin. A hospital patientat risk of thrombosis and thromboembolism is treated with ananticoagulant, warfarin, which prevents blood clots from forming butdosing must be monitored closely to avoid excessive bleeding and yetprevent clots from forming. Instead of measuring clotting time with anex vivo blood test the concentration of warfarin in the blood can bemonitored by scheduled eye interrogations. Warfarin (also known asCoumadin) displays a characteristic IR spectrum with absorption peaks at3200 cm⁻¹ and 1747 cm⁻¹ (see e.g., the Data Sheet: “Warfarin IRSpectrum” in “Characterisation” which is incorporated herein byreference). After a loading dose of warfarin is administered the eyeinterrogation system is scheduled to attract the patient's gaze anddetermine the warfarin concentration in the blood vessels of the eyeevery 4 hours. Warfarin concentrations determined by mid-infraredspectroscopy in the eye are correlated to blood clotting timesdetermined ex vivo and stored in a reference database. If the warfarinconcentration and the corresponding clotting time are outside safeboundaries the patient's physician is notified and the dose of warfarinis adjusted. Data on the scheduled interrogation times and correspondingwarfarin concentrations is stored in a database for analysis by thephysician or pharmacist to predict future doses of warfarin.

Eye interrogation system 3700 may also include sources and sensors todetect other physiological parameters to monitor the patient's healthaccording to a predetermined schedule. For example the eye interrogationsystem may be scheduled to measure the patient's heart rate, respirationrate and temperature. The corresponding components includinginterrogation sources and detectors are described above in Example 2.The health parameter data obtained from the eye interrogation system isanalyzed by signal processing circuitry 3708 and provided to healthcaregivers. Moreover the health parameters may be consolidated toprovide an overview of the patient's health over a time frame determinedby the scheduled eye interrogations.

FIG. 38 is a flow diagram of a method 3800 of measuring information froman eye of a subject, which includes delivering an interrogation signalto the eye of the subject with an interrogation signal source 3802;detecting a response signal from the eye of the subject with a responsesignal sensor; processing a response signal sensed from the eye of thesubject to determine a physiological parameter from the response signal3804; determining whether the eye of the subject is in alignment withrespect to at least one of the interrogation signal source and theresponse signal sensor 3806; determining a physiological parameter ofthe subject from the response signal detected from the eye of thesubject when the eye of the subject is in alignment with respect to theat least one of the interrogation signal source and the response signalsensor 3808; and collecting samples of the physiological parameteraccording to a schedule under the direction of a scheduling controller3810.

As shown in FIG. 39, a method 3900 also includes transmitting at leastone of information regarding the subject, information regarding thesystem used for determining the physiological parameter, or informationregarding the physiological parameter to a data processing system 3902.In various embodiments, the method may include receiving at least one ofinformation regarding the subject, information regarding the system usedfor determining the physiological parameter, or information regardingthe physiological parameter from a data processing system 3904; orsharing at least one of information regarding the subject, informationregarding the system used for determining the physiological parameter,or information regarding the physiological parameter between two or moredata processing systems 3906.

Method 3900 may include determining the identity of the subject 3908,for example, through the use of facial recognition 3910 or retinalrecognition 3912, or comparing login information entered by the subjectwith login information in a registry 3914. As indicated at 3916, in someaspects the method may include collecting samples of the physiologicalparameter only when the identity of the subject meets a selectioncriterion. For example, once the identity of the subject has beendetermined, the identity of the subject may be compared with an identityof one or more approved subjects, and if the identity matches anidentity of an approved subject, the selection criterion is met.

In an embodiment shown in FIG. 40, a method 4000 includes collecting apredetermined number of samples of the physiological parameter during asampling period 4002. The method may include collecting samples of thephysiological parameter with at least a minimum sampling intervalbetween samples 4004. The method may include modifying the procedure forcollecting a sample of the physiological parameter if a predeterminednumber of samples meeting an acceptance criterion has not been collectedwithin a predetermined portion of the sampling period 4006. Modifyingthe procedure for collecting a sample of the physiological parameter mayinclude modifying the acceptance criterion 4008, for example asignal-to-noise ratio criterion 4010 or sampling interval criterion4012, as discussed herein above. In another aspect, modifying theprocedure for collecting a sample of the physiological parameter mayinclude modifying the schedule, as indicated at 4014.

As depicted in FIG. 41, in an embodiment, a method 4100 includesreceiving a gaze signal containing information indicative of a gazedirection of an eye of the subject 4102; determining the gaze directionof the eye of the subject based upon the gaze signal 4104; determiningwhether the eye of the subject is in alignment with respect to at leastone of the interrogation signal source and the response signal sensorbased at least in part upon the gaze direction 4106. Method 4100 mayinclude moving at least one of the interrogation signal source and theresponse signal sensor into alignment with the eye of the subject if apredetermined number of samples meeting an acceptance criterion has notbeen collected within a predetermined portion of the sampling period4108. In one aspect, method 4100 includes activating a gaze attractoradapted to attract the gaze of the subject and bring the eye of thesubject into alignment with at least one of the interrogation signalsource and the response signal sensor if a predetermined number ofsamples meeting an acceptance criterion has not been collected within apredetermined portion of the sampling period 4110.

As shown in FIG. 42, in method 4200 delivering the interrogation signalincludes delivering a pulsed interrogation signal 4202. The method mayalso include gating detection of the response signal relative to thepulsed interrogation signal 4204. The method may include detectingmultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal 4206, and mayinclude combining the multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal, for example by summing the multiple response signals 4208,averaging the multiple response signals 4210, determining a movingaverage of the multiple response signals 4212, and or determining aweighted sum of the multiple response signals 4214.

As shown in FIG. 43, in method 4300 delivering an interrogation includesdelivering an interrogation signal containing multiple wavelengths oflight 4302. The method may include detecting a first response signalproduced by the eye of the subject responsive to a first wavelengthcomponent of the interrogation signal, and detecting a second responsesignal produced by the eye of the subject responsive to a secondwavelength component of the interrogation signal 4304. In an embodiment,a method includes delivering a first interrogation signal having a firstoptical wavelength and a second interrogation signal having a secondoptical wavelength 4306. The method may include determining thephysiological parameter of the subject by comparing a first responsesignal sensed from the eye of the subject in response to the firstinterrogation signal and a second response signal sensed from the eye ofthe subject in response to the second interrogation signal 4308. In anembodiment, the method includes delivering the first interrogationsignal simultaneously with respect to the second interrogation signal4310. In another embodiment, the method includes delivering the firstinterrogation signal sequentially with respect to the secondinterrogation signal 4312.

In another aspect, as shown in FIG. 44, a method 4400 includes sendingan output signal relating to the determined physiological parameter toan output structure 4402, which may include, for example, a datatransmission structure 4404, data storage structure 4406, display 4408,audio output 4410, or visual output 4412. The method may include sendingthe output signal to a display adapted to display information relatingto the determined physiological parameter 4414. The method may includesending the output signal to a video monitor 4416, computer display4418, video game display 4420, telephone display 4422, or dataprocessing device 4424.

As shown FIG. 45, in a method 4500, a measurement of a substance in theblood of the subject, as indicated at 4512, and in some embodiments, thephysiological parameter is a measurement of a substance in an aqueoushumor of the subject, as indicated at 4504. The physiological parametercan be a measurement of oxygen 4506, glucose 4508, a salt 4510, aprotein 4512, a lipid 4514, a gas 4516, a hormone 4518, or a drug 4520.The physiological parameter can be a pulse rate 4522, a blood flow 4524,or a temperature 4526.

As shown in FIG. 46, a method 4600 may include determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at one or more set times 4602, determiningthe physiological parameter of the subject from the response signaldetected from the eye of the subject at a set time interval 4604, ordetermining the physiological parameter of the subject from the responsesignal detected from the eye of the subject according to a programmedschedule 4606. In an embodiment, a programmed schedule can bepersonalized for the subject 4608. The programmed schedule can beselected from among at least two pre-programmed schedules based upon atleast one attribute of the subject 4610, or selected from among at leasttwo pre-programmed schedules based upon the physiological parameter4612.

As shown in FIG. 47, a method 4700 includes reporting informationregarding the physiological trend to an interested party 4704, forexample, one or more of the subject, a medical service provider, afamily member, a legal guardian or a legal representative 4706. In anembodiment, method 4700 includes comparing the physiological parameterdetermined from the response signal to a previous measurement of aphysiological parameter to determine a physiological trend 4708. Method4700 may also include reporting information regarding the physiologicaltrend to an interested party 4710, for example one or more of thesubject, a medical service provider, a family member, a legal guardianor a legal representative 4712.

In an aspect, method 4700 includes utilizing the physiological parameterdetermined from the response signal to assess an emotional state of thesubject 4714 or utilizing the physiological parameter determined fromthe response signal to assess the alertness of the subject 4716. In anaspect, method 4700 includes utilizing the physiological parameterdetermined from the response signal in a medical or health-relatedapplication 4718. In another aspect, method 4700 includes utilizing thephysiological parameter determined from the response signal in abusiness or security application 4720.

A method 4800 shown in FIG. 48 also includes presenting an input to thesubject 4802; and utilizing the physiological parameter determined fromthe response signal to determine a response of the subject to the input4804. The input can include information 4806 (including, but not limitedto advertising information 4808, marketing research information 4810,print information 4812, or video information 4814). The input mayinclude an auditory stimulus 4816, visual stimulus 4818, tactilestimulus 4820, olfactory stimulus 4822, gustatory stimulus 4824, thermalstimulus 4826, neural stimulus 4828, a drug 4830, a pharmaceutical 4832,a nutraceutical 4834, or a nutrient 4836.

As shown in FIG. 49, a method 4900 includes delivering an interrogationsignal to the eye of the subject with an interrogation signal source anddetecting a response signal from the eye of the subject with a responsesignal sensor may be performed unobtrusively 4902, as described hereinabove. In some embodiments, delivering an interrogation signal to theeye of the subject with an interrogation signal source and detecting aresponse signal from the eye of the subject with a response signalsensor may be performed without detection by the subject 4904. Invarious aspects, the method may include receiving an input indicative ofan instruction from the subject or representative of the subject forinformation to be measured 4906, receiving an input indicative ofauthorization from the subject or representative of the subject forinformation to be measured 4908, or receiving an input indicative ofinformed consent from the subject or representative of the subject forinformation to be measured 4910.

FIG. 50 depicts an article of manufacture 5000 that includes one or morenon-transitory machine-readable data storage media 5002 bearing one ormore instructions 5004 for performing a method as shown in FIG. 38,including delivering an interrogation signal to the eye of the subjectwith an interrogation signal source; detecting a response signal fromthe eye of the subject with a response signal sensor; processing aresponse signal sensed from the eye of the subject to determine aphysiological parameter from the response signal; determining whetherthe eye of the subject is in alignment with respect to at least one ofthe interrogation signal source and the response signal sensor;determining a physiological parameter of the subject from the responsesignal detected from the eye of the subject when the eye of the subjectis in alignment with respect to the at least one of the interrogationsignal source and the response signal sensor; and collecting samples ofthe physiological parameter according to a schedule under the directionof a scheduling controller.

In one aspect, the one or more non-transitory machine-readable datastorage media 5002 bear one or more instructions performing method stepsas shown in FIG. 39, e.g. instructions for transmitting at least one ofinformation regarding the subject, information regarding the system usedfor determining the physiological parameter, or information regardingthe physiological parameter to a data processing system. The datastorage media 5002 bear one or more instructions for receiving at leastone of information regarding the subject, information regarding thesystem used for determining the physiological parameter, or informationregarding the physiological parameter from a data processing system.Data storage media 5002 may bear one or more instructions for sharing atleast one of information regarding the subject, information regardingthe system used for determining the physiological parameter, orinformation regarding the physiological parameter between two of moredata processing systems. Data storage media 5002 may bear one or moreinstructions for determining the identity of the subject, for examplethrough the use of facial recognition or retinal recognition, or bycomparing login information entered by the subject with logininformation in a registry, also as shown in FIG. 39.

The data storage media 5002 may bear one or more instructions forperforming a method as shown in FIG. 40, including collecting apredetermined number of samples of the physiological parameter during asampling period. In an aspect data storage media 5002 bear one or moreinstructions for collecting samples of the physiological parameter withat least a minimum sampling interval between samples. Data storage media5002 may bear one or more instructions for modifying the procedure forcollecting a sample of the physiological parameter if a predeterminednumber of samples meeting an acceptance criterion has not been collectedwithin a predetermined portion of the sampling period. In anotheraspect, data storage media bear one or more instructions for modifyingthe procedure for collecting a sample of the physiological parameterincludes modifying the acceptance criterion. The acceptance criterionmay include, for example, a signal-to-noise ratio criterion, or asampling interval criterion.

Data storage media 5002 may bear one or more instructions 5004 forperforming a method as shown in FIG. 41, including receiving a gazesignal containing information indicative of a gaze direction of an eyeof the subject; determining the gaze direction of the eye of the subjectbased upon the gaze signal; determining whether the eye of the subjectis in alignment with respect to at least one of the interrogation signalsource and the response signal sensor based at least in part upon thegaze direction; and determining whether the eye of the subject is inalignment with respect to at least one of the interrogation signalsource and the response signal sensor. Data storage media 5002 may bearone or more instructions for determining the physiological parameterfrom the response signal when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor. This may include, for example, one or moreinstructions for causing alignment of the eye of the subject withrespect to the at least one of the interrogation signal source and theresponse signal sensor if a predetermined number of samples meeting anacceptance criterion has not been collected within a predeterminedportion of the sampling period; one or more instructions for causing thealignment of the eye of the subject with respect to the at least one ofthe interrogation signal source and the response signal sensor by movingat least one of the interrogation signal source and the response signalsensor into alignment with the eye of the subject; or bear one or moreinstructions for: causing the alignment of the eye of the subject withrespect to the at least one of the interrogation signal source and theresponse signal sensor by activating a gaze attractor adapted to attractthe gaze of the subject to thereby cause the eye of the subject to moveinto alignment with at least one of the interrogation signal source andthe response signal sensor.

Data storage media 5002 may include one or more instructions forperforming a method as shown in FIG. 42, including one or moreinstructions for delivering the interrogation signal includes deliveringa pulsed interrogation signal. In one aspect, the data storage media maybear one or more instructions for gating detection of the responsesignal relative to the pulsed interrogation signal. In one aspect, thedata storage media may bear one or more instructions for detectingmultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal. The data storagemedia may in addition bear one or more instructions for combining themultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal by summing themultiple response signals, by averaging the multiple response signals,by determining a moving average of the multiple response signals, and/orby determining a weighted sum of the multiple response signals, forexample.

Data storage media 5002 may bear one or more instructions for performinga method as shown in FIG. 43. In an embodiment, data storage media 5002bear one or more instructions for delivering an interrogation signalcontaining multiple wavelengths of light. The data storage media maythen also bear one or more instructions for detecting a first responsesignal produced by the eye of the subject responsive to a firstwavelength component of the interrogation signal, and detecting a secondresponse signal produced by the eye of the subject responsive to asecond wavelength component of the interrogation signal. In anotherembodiment, the data storage media bear one or more instructions fordelivering a first interrogation signal having a first opticalwavelength and a second interrogation signal having a second opticalwavelength. Data storage media may bear one or more instructions fordetermining the physiological parameter of the subject by comparing afirst response signal sensed from the eye of the subject in response tothe first interrogation signal and a second response signal sensed fromthe eye of the subject in response to the second interrogation signal.

Data storage media 5002 may bear one or more instructions for performinga method as shown in FIG. 44. In one aspect, data storage media bear oneor more instructions for delivering the first interrogation signalsimultaneously with respect to the second interrogation signal. Inanother aspect, data storage media bear one or more instructions fordelivering the first interrogation signal sequentially with respect tothe second interrogation signal. In various embodiments, the datastorage media bear one or more instructions for: sending an outputsignal relating to the determined physiological parameter to an outputstructure, which may be, for example, a data transmission structure,data storage structure, a display, an audio output, or a visual output.In an aspect, data storage media 5002 bear one or more instructions forsending the output signal to a display adapted to display informationrelating to the determined physiological parameter. In some embodiments,data storage media bear one or more instructions for sending the outputsignal to a video monitor, a computer display, a video game display, atelephone display, or to a data processing device.

Data storage media 5002 may include instructions relating todetermination of various different physiological parameters, including,for example, a measurement of a substance in the blood of the subject,such as oxygen, glucose, a salt, a protein, or a lipid, a measurement ofa substance in an aqueous humor of the subject, such as oxygen, glucose,a salt, a protein, or a lipid, a hormone, a drug, a pulse rate, ameasurement of glycosylated hemoglobin, a temperature, a bodytemperature, a measurement of blood flow, a measurement of a substancein the eye of the subject.

In an aspect, data storage media 5002 bear one or more instructions forperforming a method as shown in FIG. 46, including determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at one or more set times. In another aspect,data storage media bear one or more instructions for determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject at a set time interval. In an aspect, datastorage media bear one or more instructions for determining thephysiological parameter of the subject from the response signal detectedfrom the eye of the subject according to a programmed schedule. Theprogrammed schedule may be personalized for the subject. The programmedschedule may be selected from among at least two pre-programmedschedules based upon at least one attribute of the subject, and/or basedupon the physiological parameter.

In an aspect, the data storage media 5002 bear one or more instructionsfor performing a method as shown in FIG. 47, including reportinginformation regarding the physiological trend to an interested party,such as the subject, a medical service provider, a family member, alegal guardian or a legal representative. In another aspect, datastorage media bear one or more instructions for comparing thephysiological parameter determined from the response signal to aprevious measurement of a physiological parameter to determine aphysiological trend. The data storage media may also bear one or moreinstructions for reporting information regarding the physiological trendto an interested party, e.g. one or more of the subject, a medicalservice provider, a family member, a legal guardian or a legalrepresentative. Data storage media may bear one or more instructions forutilizing the physiological parameter determined from the responsesignal to assess an emotional state of the subject, and/or one or moreinstructions for utilizing the physiological parameter determined fromthe response signal to assess the alertness of the subject. Data storagemedia may bear one or more instructions for utilizing the physiologicalparameter determined from the response signal in a medical orhealth-related application, or one or more instructions for utilizingthe physiological parameter determined from the response signal in abusiness or security application.

In one aspect, data storage media 5002 bear one or more instructions forperforming a method as shown in FIG. 48, including presenting an inputto the subject; and utilizing the physiological parameter determinedfrom the response signal to determine a response of the subject to theinput. For example, the input may include information (advertisinginformation, marketing research information, print information, or videoinformation, for example), an auditory stimulus, a visual stimulus, atactile stimulus, an olfactory stimulus, a gustatory stimulus, a thermalstimulus, a neural stimulus, a drug, a pharmaceutical, a nutraceutical,or a nutrient.

Data storage media 5002 may include instructions 5004 for performing amethod as shown in FIG. 49, including delivering an interrogation signalto the eye of the subject with an interrogation signal source anddetecting a response signal from the eye of the subject with a responsesignal sensor are performed unobtrusively, and/or without detection bythe subject. Data storage media may include one or more instructions forreceiving an input indicative of an instruction from the subject orrepresentative of the subject for information to be measured, receivingan input indicative of authorization from the subject or representativeof the subject for information to be measured, or receiving an inputindicative of informed consent from the subject or representative of thesubject for information to be measured.

FIG. 51 depicts a system 5100 for sensing information from an eye 5102of a subject 5104, which includes an interrogation signal source 5106for delivering an interrogation signal to eye 5102 of a subject 5104; aresponse signal sensor 5110 for sensing a response signal produced bythe eye 5102 of the subject 5104 responsive to the interrogation signal;a gaze attractor 5120 adapted to attract the gaze of the subject 5104 tothereby cause the eye of the subject to move into alignment with atleast one of the interrogation signal source 5106 or the response signalsensor 5110; and signal processing circuitry 5122 including: a responsesignal processor 5124 configured to process a response signal sensedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source 5106or the response signal sensor 5110 to determine a physiologicalparameter 5126 from the response signal. System 5100 is discussedconnection with an example of an eye interrogation system incorporatedinto a treadmill 5128, for monitoring and display of physiologicalparameters. However, various other implementations of system 5100 willbe apparent to a person having ordinary skill in the art, based on thedisclosure presented herein.

EXAMPLE 4 An Eye Interrogation System on a Treadmill to Monitor andDisplay Physiological Parameters

A noncontact eye interrogation system 5100 which measures and displaysphysiological parameters 5126 to a runner is built into treadmill 5128.The eye interrogation system includes gaze attraction and trackingcomponents to align the runner's eyes with an interrogation signalsource 5106 and a response signal sensor 5120. The system includes asignal processing circuitry to activate the interrogation source 5106and response signal sensor 5110 during exercise and to obtainphysiological data from the detected signals. The noncontact eyeinterrogation system 5100 unobtrusively monitors and displays heartrate, respiration rate, body temperature, and oxygen saturation in theblood. In the example shown in FIG. 51, the system may include signalprocessing circuitry (including hardware and software) that causes thephysiological parameter 5126 to be displayed on a liquid crystal display(LCD) 5130 display on the treadmill 5128.

To align the runner's eyes with the interrogation signal source 5106,gaze attractor 5120 is incorporated in the system. A gaze attractor 5120may be a light that draws attention while the runner exercises, as shownin FIG. 51. For example, the eye interrogation system may have a LEDgaze attractor 5120 a which flashes and draws the runner's gaze to thevicinity of interrogation source 5106 and response signal sensor 5110when a physiological parameter 5126 is to be measured. Signal processingcircuitry 5122 may activate the LED 5120 a and interrogation systemaccording to a preset schedule, e.g. every 10 minutes, or according tothe runner's preset preferences. A gaze tracking system is used todetect when the runner looks at the LED gaze attractor 5120 a,interrogation signal source 5106 and response signal sensor 5110. Thegaze tracking system is comprised of a gaze tracking stimulus source5134 that is an IR light source 5134 a and a gaze signal sensor 5136that is an IR camera 5136 a which detects the reflection of IR lightfrom the eyes of the runner. Eye position, eye rotation, eye gazeposition against screen, pupil diameter and eye vergence distance may bemonitored. The gaze tracking system includes software and circuitryforming gaze signal processor 5138 to analyze the gaze tracking data andalignment detector 5140 to detect alignment of the runner's gaze withthe interrogation source and/or the interrogation detectors. Alignmentof the runner's eyes with the interrogation signal source 5106 andresponse signal sensor 5110 triggers activation of the interrogationsignal source 5106 by the signal processing circuitry 5122.

To monitor the runner's heart rate 5126 a and respiration 5126 b the eyeinterrogation system is equipped with an interferometry system thatdetects movement of an individual's chest wall. Construction of aninterferometer, data acquisition systems and signal processingalgorithms to determine heart rate and respiration are described (seee.g., U.S. Pat. No. 7,272,431 issued to McGrath on Sep. 18, 2007 andMikhelson et al., IEEE Transactions on Biomedical Engineering, 58:1671-1677, 2011 which are incorporated herein by reference). For examplea continuous wave millimeter-wave interferometer is constructed integralto the eye interrogation system. A continuous wave 94-GHz signal isgenerated by a cavity-tuned Gunn diode oscillator 5106 a and transmittedat the runner with a Gaussian (quasi-optical) antenna with a lens thatresults in a far-field starting at approximately 0.5 meter and a beamdivergence of approximately 1.5 degrees. The gaze tracking system (seeabove) is used to establish alignment of the oscillator and antenna onthe runner's chest and to signal activation of the interferometer.Interferometer components include a Gunn diode oscillator 5106 a (94GHz) a circulator, a Gaussian antenna and beam splitters and mixers. Toacquire the reflected wave signals a 24 bit data acquisition device (DAQ5110 a) (e.g., “24-Bit, 102.4 kS/s, 8 and 4-Channel Dynamic SignalAcquisition” available from National Instruments, Austin, Tex.; see theData sheet: “DAQ Device” which is incorporated herein by reference) isused with LabView data acquisition software. The vibration signals maybe processed with programs written in MATLAB to derive chestdisplacements (respiration) and heart beats from the reflected wavesignals (see e.g., Mikhelson et al., Ibid.). Heart rate and respirationdata are analyzed and displayed by system circuitry and software. Thedata may be displayed on a LCD on the treadmill and the runner may bealerted when maximum heart rate is exceeded. Abnormal heart rate mayalso be transmitted to a healthcare worker or medic.

To monitor the runner's temperature 5126 c an infrared thermometer isincorporated in the eye interrogation system which remotely measurestemperature in the eye. Following alignment of the runner's eye with theinfrared thermometer the thermometer is activated. An infraredthermometer comprised of a detector, collecting optical system (e.g.,lens and filter) and signal processing circuitry is incorporated in theeye interrogation system. The filter limits the spectrum of infraredradiation detected and the lens' optical characteristics determine thetarget size within the eye and the allowed distance from the runner'seye. The detector converts infrared energy into an electrical signalwhich is amplified and processed by the associated signal processors tocalculate temperature of the eye. An infrared thermometer suitable forsensitive temperature measurement (i.e., approximately 0.1 degreeCentigrade) that may be targeted to the iris/pupil region or to thesclera is described (see e.g., U.S. Pat. No. 5,115,815 issued to Hansenon May 26, 1992 which is incorporated herein by reference). For examplean infrared camera 5110 c may be used to measure corneal temperature(see e.g., Kessel et al., Investigative Ophthalmology and Visual Science51: 6593-6597, 2010 which is incorporated herein by reference). Aninfrared camera 5110 c with a focal plane array detector, thermalsensitivity ≦0.09 degrees C. and an accuracy of 0.1 degrees C. isavailable from Fluke Corp., Everett, Wash. (see e.g., “FlukeIndustrial/Electrical Thermal Imagers, Models: Ti25 and Ti10” Datasheetwhich is incorporated herein by reference). To summarize, duringexercise on the treadmill the LED gaze atrractor 5120 a lights up andthe gaze tracking system detects alignment of the runners' eye with theinfrared thermometer. Next the system controller activates the infraredthermometer and signal processors determine eye temperature from theinfrared radiation. The runner's temperature data are displayed ondisplay 5130 of treadmill 5128 and may be transmitted to a remotedevice, e.g., a computer (not shown) for analysis and storage. Forexample, analysis of corneal eye temperatures shows that they may becorrelated with core body temperatures (see e.g., Kessel et al., Ibid.).If safe core body temperatures are exceeded the eye interrogation systemmay alert the runner on the system LCD and alert health care workers byemail.

To measure the runner's oxygenation of hemoglobin 5126 d, the eyeinterrogation system may also incorporate an interrogation light sourceand response signal sensor to measure oxyhemoglobin and deoxyhemoglobinin the fundus of the eye. An apparatus and methods to measureoxyhemoglobin and deoxyhemoglobin in the eye are described (see e.g.U.S. Pat. No. 6,149,589 issued to Diaconu et al. on Nov. 21, 2000 whichis incorporated herein by reference). An interrogation source 5106 thatgenerates wavelengths between 450 nm and 850 nm is integrated in the eyeinterrogation system (see FIG. 8). For example a tungsten halogen lightsource with a wavelength range of 360 nm to 2000 nm in wavelength isavailable from Ocean Optics, Dunedin, Fla. See e.g., the SpecificationSheet: “HL-2000 Tungsten Halogen Light Sources” which is incorporatedherein by reference. The optical system may include lenses and filtersto focus and limit the wavelength spectrum of the light beam. Lightreflected from the eye is detected by a response signal sensor 5110which is also located in the interrogation system. The response signalsensor 5100 may include an optical collector and a spectrometer todetermine the reflected spectrum. For example the collector may includea collimating lens assembly with a single aspheric lens with a field ofview of approximately 45 degrees (e.g., a 74-DA Collimating Lens(200-2000 nm) is available from Ocean Optics, Dunedin, Fla.). The lensattaches to a spectrometer for increased light throughput and collectscollimated light in a straight path of open air and focuses it on to aspectrometer's slit. The spectrometer may be a fiber optic spectrometerwith a CCD-array detector and an analog to digital converter withprogrammable circuitry. For example a miniature fiber optic spectrometerwith a 2048-element CCD-array detector with a range of 200-1100 nm and agrating with a spectral range of 625 nm with best efficiency from 530 nmto 1100 nm is available from Ocean Optics, Dunedin, Fla. (see e.g., theSpecification Sheet: USB2000+ Miniature Fiber Optic Spectrometer whichis incorporated herein by reference). The spectrometer has amicrocontroller and USB connector to allow activation and programming ofthe spectrometer by a computer.

The spectrum of reflected light emanating from the fundus of the eye isdetected by the CCD array and electronic signals are processed to derivethe absorption spectrum for the runner's eye. Absorption peaks between500 nm and 600 nm may be analyzed to determine the fraction ofoxygenated hemoglobin (see e.g., Dianconu et al., Ibid.). Computation ofthe reflectance spectra and comparison to reference spectra foroxygenated and deoxygenated hemoglobin permits calculation of thepercentage oxygenation of total hemoglobin in the runner's eye. Thepercent oxyhemoglobin may be displayed on the LCD display 5130 of thetreadmill 5128 and the runner may be alerted if the percentage ofoxygenated hemoglobin falls below healthy levels. The percentoxyhemoglobin data may also be sent to healthcare workers or exercisephysiologists.

In an embodiment, system includes a gaze signal sensor 5136 adapted forreceiving a gaze signal containing information indicative of a gazedirection of an eye of the subject; a gaze signal processor 5138configured to determine the gaze direction of the eye of the subjectbased upon the gaze signal; and an alignment detector 5140 configured todetermine whether the eye of the subject is in alignment with respect toat least one of the interrogation signal source 5106 or the responsesignal sensor 5110 based at least in part upon the gaze direction.

In an embodiment, the response signal sensor 5110 is adapted to sense aresponse signal from an interior of the eye of the subject responsive tothe interrogation signal, for example, from a lens, aqueous humor,vitreous humor, and/or retina of the eye of the subject responsive tothe interrogation signal.

As depicted in FIG. 51, gaze signal sensor 5136 and the response signalsensor 5110 can be different sensors. However, in some embodiments, gazesignal sensor 5136 and the response signal sensor 5110 are the samesensor. In some embodiments, gaze signal sensor 5136 includes aninfrared camera or CCD camera.

System 5100 can include an interrogation signal source 5106 thatincludes a broad spectrum light source and response signal sensor 5110that includes a spectrometer based on a CCD array. In other embodiments,interrogation signal source 5106 includes a near-infrared light sourceand response signal sensor 5110 includes a near-infrared camera,interrogation signal source 5106 includes a tunable laser source andresponse signal sensor 5110 includes a Raman spectrometer based on a CCDcamera, interrogation signal source 5106 includes a mid-infrared lightsource and the response signal sensor 5110 includes a mid-infrareddetector, or interrogation signal source 5106 includes a tunable lasersource and response signal sensor 5110 includes a broad spectrumpyroelectric detector, for example.

In some embodiments, the response signal is indicative of a feature ofthe vasculature of the eye of the subject, or indicative of a biometricidentification of the subject.

As shown in FIG. 51, system 5110 can include at least one gaze trackingstimulus source 5134 adapted to deliver a gaze tracking stimulus to atleast an eye of a subject, wherein the gaze signal is produced inresponse to the gaze tracking stimulus. In one embodiment, gaze trackingstimulus source 5134 includes an infra-red source. In connectiontherewith, gaze signal sensor 5136 includes an infra-red sensor. Inanother embodiment, gaze tracking stimulus source 5134 can include anear infra-red source, and gaze signal sensor 5136 can include a nearinfra-red sensor.

Gaze tracking stimulus source 5134 may include a single light source, ora plurality of light sources. Gaze signal sensor 5136 can include anoptical sensor, optical sensor array, camera, or plurality of gazesignal sensors.

In an embodiment, interrogation signal source 5106 is adapted to producelight having a first polarization, and the response signal sensor isadapted to detect light having a second polarization, wherein the firstpolarization and the second polarization are the same. In an embodiment,interrogation signal source is adapted to produce light having a firstpolarization, and the response signal sensor is adapted to detect lighthaving a second polarization, wherein the first polarization and thesecond polarization are different. See, e.g. discussion in connectionwith FIG. 12.

In an embodiment, interrogation signal source 5106 is adapted to delivera pulsed interrogation signal. At least one of the response signalsensor 5110 and signal processing circuitry 5122 is configured to gatedetection of the response signal relative to the pulsed interrogationsignal. Signal processing circuitry 5122 may be configured to combinemultiple response signals produced by the eye of the subject in responseto multiple pulses of the pulsed interrogation signal, e.g., by summingor averaging the multiple response signals, or determining a movingaverage or weighted sum of the multiple response signals. See, e.g.,discussion in connection with FIG. 6.

In an embodiment, the interrogation signal source 5106 is adapted todeliver an interrogation signal containing multiple wavelengths oflight, as discussed generally in connection with FIG. 7. System 5100 mayinclude at least a first response signal sensor configured to sense afirst response signal produced by the eye of the subject responsive to afirst wavelength component of the interrogation signal, and a secondresponse signal sensor configured to sense a second response signalproduced by the eye of the subject responsive to a second wavelengthcomponent of the interrogation signal. In an embodiment, system 5100includes at least a first interrogation signal source configured todeliver a first interrogation signal having a first optical wavelengthand at least a second interrogation signal source configured to delivera second interrogation signal having a second optical wavelength. Signalprocessing circuitry 5100 may then be configured to process a firstresponse signal sensed from the eye of the subject in response to thefirst interrogation signal and a second response signal sensed from theeye of the subject in response to the second interrogation signal bycomparing the first and second response signals to determine thephysiological parameter. System can be configured to deliver the firstinterrogation signal simultaneously with respect to the secondinterrogation signal, or sequentially with respect to the secondinterrogation signal. Further details regarding this approach areprovided in connection with FIG. 7.

In some embodiments, interrogation signal source 5106 and the responsesignal sensor 5110 are co-aligned. In other embodiments, interrogationsignal source 5106 and the response signal sensor 5110 are separatelyaligned and located.

System 5100 also can also include an output structure 5140 adapted tooutput a signal relating to the determined physiological parameter 5126.Output structure may include, for example, data storage structure,display, audio output, or visual output, as discussed herein above, anddepicted, e.g., in FIG. 8. System may include a display (e.g. display5130) adapted to display information relating to the determinedphysiological parameter 5126. The display can be a video monitor,computer display, video game display, telephone display, or terminal ofa data processing device, for example. In various embodiments, thedisplay 5130 can be incorporated in a wearable item, an article offurniture, an article of medical or health-care related equipment, anarticle of exercise equipment (as illustrated in FIG. 51), or a vehicle.Examples of such displays are described in greater detail herein above.

Physiological parameter 5126 may be a measurement of oxygenation, bloodglucose, heart rate, glycosylated hemoglobin, temperature, bodytemperature, blood flow, or a substance in the eye of the subject.

In some embodiments, gaze attractor 5120 includes a visual stimulussource 5142 for delivering a visual stimulus to attract the gaze of thesubject. For example, the visual stimulus source 5120 can be a mirror,light source (such as an LED), or video display. In one aspect, thevisual stimulus source 5120 is adapted for attachment to various typesof displays or other items that the subject may look at, or toward whicha subject may turn his or her head or direct his or her gaze during useof, attention to, or interaction with the item. Items to which a visualstimulus source may be attached include a video display, computerdisplay, video game display, television, terminal of a data processingdevice, smart phone, smart book, book, article of furniture, article ofmedical equipment, or article of exercise equipment.

Visual stimulus source 5142 may be adapted to produce a visual stimulusthat differs from a visual background in some manner, for example, avisual stimulus that includes a different light intensity, differentoptical wavelength, different temporal pattern of light intensity,different temporal pattern of optical wavelength, different spatialpattern of light intensity, or different spatial pattern of opticalwavelength relative to a visual background. Visual stimulus source 5142may be adapted to produce a visual stimulus that includes an image, amoving image, or text. In one aspect, at least one visual stimulussource 5142 is configured such that when the gaze of the subject isdirected toward the visual stimulus the eye of the subject will bebrought into alignment with respect to the at least one of theinterrogation signal source 5106 or the response signal sensor 5110.

In another aspect, gaze attractor 5120 includes at least one auditorystimulus source 5144 for delivering a localized auditory stimulus toattract the gaze of the subject. At least one auditory stimulus source5144 can be configured such that when the gaze of the subject isdirected toward the auditory stimulus the eye of the subject will bebrought into alignment with respect to the at least one of theinterrogation signal source 5106 or the response signal sensor 5110. Inan embodiment, gaze attractor 5120 includes at least one auditorystimulus source 5144 and at least one visual stimulus source 5142configured to deliver at least one auditory stimulus and at least onevisual stimulus in sequence. In an embodiment, gaze attractor includesat least one auditory stimulus source 5144 and at least one visualstimulus source 5142 configured to deliver at least one auditorystimulus and at least one visual stimulus simultaneously.

FIG. 52 is a schematic diagram of a system 5200 for controlling thesensing of information from an eye of a subject, including signalprocessing circuitry 5122 including: a gaze attractor controller 5202adapted to drive a gaze attractor 5120 to cause the eye of the subjectto move into alignment with at least one of an interrogation signalsource 5106 or the response signal sensor 5110; a response signal input5204 adapted to receive a response signal sensed from the eye of thesubject by a response signal sensor 5110 responsive to delivery of aninterrogation signal to the eye of the subject; and a response signalprocessor 5124 configured to process a response signal sensed from theeye of the subject when the eye of the subject is in alignment withrespect to the at least one of the interrogation signal source 5106 orthe response signal sensor 5110 to determine a physiological parameter5126 from the response signal.

System 5200 may further include a gaze signal input 5206 adapted toreceive a gaze signal containing information indicative of a gazedirection of the eye of the subject sensed from at least an eye of thesubject; a gaze signal processor 5138 configured to determine the gazedirection of the eye of the subject based upon the gaze signal; and analignment detector 5140 configured to determine whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source 5106 or the response signal sensor 5110based at least in part upon the gaze direction.

Response signal processor 5124 can be configured to process the responsesignal to determine a feature of the vasculature of the eye of thesubject, or to determine a biometric identification of the subject, asdiscussed herein above.

In one aspect, gaze attractor controller 5202 is adapted to drive avisual stimulus source 5142 for delivering a visual stimulus to attractthe gaze of the subject. The visual stimulus source may be, for example,a mirror, a light source, or a video display. In one aspect, gazeattractor controller 5202 is adapted to drive the visual stimulus sourceto produce a visual stimulus that differs from a visual background,which may be, for example, a visual stimulus that includes a differentlight intensity, different optical wavelength, different temporalpattern of light intensity, different temporal pattern of opticalwavelength, different spatial pattern of light intensity, or differentspatial pattern of optical wavelength relative to a visual background.

Gaze attractor controller 5202 may be adapted to drive the visualstimulus source 5142 to produce a visual stimulus that includes animage, a moving image, or text. In another aspect, gaze attractorcontroller 5202 is adapted to drive at least one auditory stimulussource 5144 for delivering a localized auditory stimulus to attract thegaze of the subject. In another aspect, gaze attractor controller 5120is adapted to drive at least one auditory stimulus source 5144 and atleast one visual stimulus source 5142 to deliver at least one auditorystimulus and at least one visual stimulus in sequence. In yet anotheraspect, gaze attractor controller 5202 is adapted to drive at least oneauditory stimulus source 5144 and at least one visual stimulus source5142 to deliver at least one auditory stimulus and at least one visualstimulus simultaneously.

In an embodiment, system 5200 includes interrogation signal controlcircuitry 5208 configured to drive production of the interrogationsignal by the interrogation signal source 5106.

In an embodiment, system includes gaze tracking stimulus controlcircuitry 5210 configured to drive production of a gaze trackingstimulus by a gaze tracking stimulus source 5134, wherein the gazetracking stimulus is adapted to cause production of the gaze signal theeye of the subject. In an embodiment, gaze tracking stimulus controlcircuitry 5210 is configured to drive production of a gaze trackingstimulus by a plurality of gaze tracking stimulus sources, e.g. asdescribed herein above. Response signal processor 5124 may be adapted toprocess a response signal sensed from an interior of the eye of thesubject responsive to the interrogation signal, e.g., from a lens,aqueous humor, vitreous humor, or retina of the eye of the subjectresponsive to the interrogation signal.

In an aspect, response signal processor 5124 is configured to processthe response signal to determine a feature of the vasculature of the eyeof the subject. In one aspect, response signal processor 5124 isconfigured to process the response signal to determine a biometricidentification of the subject.

Gaze signal input 5206 and response signal input 5204 can be separateinputs, as depicted in FIG. 52, or the same input, for example as inFIG. 4. In an embodiment, gaze signal input 5206 is adapted to receive asignal from a camera.

In an embodiment, signal processing circuitry 5122 includes a pluralityof gaze signal inputs (generally as depicted in FIG. 12) adapted toreceive a plurality of gaze signals containing information indicative ofa gaze direction of the eye of the subject sensed from at least an eyeof the subject.

In an embodiment, response signal processor 5124 is configured toprocess the response signal by determining a first response signal at afirst polarization, determining a second response signal at a secondpolarization, and comparing the response signal determined at the firstpolarization to the response signal determined at the secondpolarization, wherein the first polarization and the second polarizationare different, as discussed herein above, e.g. in connection with FIG.12.

Response signal processor 4125 can be configured to process the responsesignal sensed from the eye of the subject by the response signal sensor5110 when the eye of the subject is in alignment with respect to the atleast one of the interrogation signal source 5106 or response signalsensor 5110 to determine a measurement of oxygenation, blood glucose,heart rate, or glycosylated hemoglobin, temperature, body temperature,blood flow, or a substance in the eye of the subject from the responsesignal, for example.

In one aspect, interrogation signal control circuitry 5208 is configuredto drive production of a pulsed interrogation signal by theinterrogation signal source, as described generally herein above inconnection with FIG. 6. Signal processing circuitry 5122 may beconfigured to gate detection of the response signal relative to thepulsed interrogation signal. Signal processing circuitry 5122 may beconfigured to combine multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal, for example by summing or averaging the multiple responsesignals, or determining a moving average or weighted sum of the multipleresponse signals.

In one aspect, a system 5200 includes interrogation signal controlcircuitry 5208 configured to drive production of a first interrogationsignal having a first optical wavelength and production of a secondinterrogation signal having a second optical wavelength. Signalprocessing circuitry 5122 may then be configured to process a firstresponse signal sensed from the eye of the subject in response to thefirst interrogation signal and a second response signal sensed from theeye of the subject in response to the second interrogation signal bycomparing the first and second response signals in order to determinethe physiological parameter. Signal processing circuitry 5122 may beconfigured to drive production of the first interrogation signalsimultaneously with respect to the second interrogation signal, orconfigured to drive production of the first interrogation signalsequentially with respect to the second interrogation signal.

In another aspect, system 5200 includes an output structure 5140 adaptedto output a signal relating to the determined physiological parameter.Output structure can include, for example, a data transmissionstructure, data storage structure, display, audio output, or visualoutput, as described herein above. In an aspect, system 5200 includes adisplay 5130 adapted to display information relating to the determinedphysiological parameter 5126.

FIG. 53 depicts a system 5300 that includes a housing 1302; aninterrogation signal source 5302 housed in the housing 1302 and adaptedfor delivering an interrogation signal to an eye of a subject, theinterrogation signal source 5302 including at least one light source5304 and at least one optical system 5306; a response signal sensor 5308housed within the housing 1302 and adapted for sensing a response signalproduced by the eye of the subject responsive to the interrogationsignal, the response signal containing information regarding aphysiological parameter of the subject; a gaze attractor 5120 adapted toattract the gaze of the subject to thereby cause the eye of the subjectto move into alignment with at least one of the interrogation signalsource 5302 or the response signal sensor 5308; an output structure 1320adapted for transmitting an output signal; mounting means 1324 adaptedfor mounting the housing with respect to a display in such a manner thatthe interrogation signal source 5302 and response signal sensor 5308 arealignable with the eye of the subject during normal use of the displayby the subject.

In an aspect, mounting means 1324 is adapted for mounting the housing1302 with respect to the display such that during normal use of thedisplay by the subject, the interrogation signal source 5302 andresponse signal sensor 5308 are positioned within the visual field of atleast one eye of the subject. In an aspect, mounting means 1324 isadapted for mounting the housing 1302 with respect to the display suchthat the interrogation signal source 5302 and response signal sensor5308 are oriented in substantially the same direction as the displaysurface of the display.

In an embodiment, system 5300 includes a gaze signal sensor 5310 adaptedfor receiving a gaze signal containing information indicative of a gazedirection of an eye of the subject. Gaze signal sensor 5310 may include,for example, an optical sensor, an optical sensor array, a camera,and/or a plurality of gaze signal sensors.

System 5300 may also include a gaze signal sensor processor 5138configured to determine the gaze direction of the eye of the subjectbased upon the gaze signal; and an alignment detector 5140 configured todetermine whether the eye of the subject is in alignment with respect toat least one of the interrogation signal source 5302 or the responsesignal sensor 5308 based at least in part upon the gaze direction.

Gaze signal sensor 5310 and the response signal sensor 5308 can be thesame sensor, or different sensors. Gaze signal sensor 5310 may include,for example, an infrared camera or a CCD camera.

In an embodiment, interrogation signal source 5302 includes a broadspectrum light source and the response signal sensor 5308 includes aspectrometer based on a CCD array. In other embodiments, interrogationsignal source 5302 includes a near-infrared light source and responsesignal sensor 5308 includes a near-infrared camera, interrogation signalsource 5302 includes a tunable laser source and the response signalsensor 5308 includes a Raman spectrometer based on a CCD camera,interrogation signal source 5302 includes a mid-infrared light sourceand response signal sensor 5308 includes a mid-infrared detector, orinterrogation signal source 5302 includes a tunable laser source andresponse signal sensor 5308 includes a broad spectrum pyroelectricdetector.

In an embodiment, system 5300 includes at least one gaze trackingstimulus source 5134 adapted to deliver a gaze tracking stimulus to atleast an eye of a subject, wherein the gaze signal is produced inresponse to the gaze tracking stimulus. In an embodiment, gaze trackingstimulus source 5134 includes an infra-red source; gaze signal sensor5310 may then include an infra-red sensor. In an embodiment, gazetracking stimulus source 5134 includes a near infra-red source and gazesignal sensor 5310 includes a near infra-red sensor. In someembodiments, gaze tracking stimulus source 5134 includes a plurality oflight sources.

In an aspect, response signal sensor 5308 is adapted to sense a responsesignal from an interior of the eye of the subject responsive to theinterrogation signal, e.g., from a lens, aqueous humor, vitreous humor,or retina of the eye of the subject. The response signal may beindicative of a feature of the vasculature of the eye of the subject, orindicative of a biometric identification of the subject, as discussedherein above. In various embodiments of the system, the physiologicalparameter is a measurement of oxygenation, blood glucose, heart rate,glycosylated hemoglobin, temperature, body temperature, blood flow, or asubstance in the eye of the subject, for example.

In an embodiment, interrogation signal source 5302 is adapted to producelight having a first polarization, and the response signal sensor 5308is adapted to detect light having a second polarization, and wherein thefirst polarization and the second polarization are the same. In anembodiment, the interrogation signal source 5302 is adapted to producelight having a first polarization, wherein the response signal sensor5308 is adapted to detect light having a second polarization, andwherein the first polarization and the second polarization aredifferent. In one aspect, interrogation signal source 5302 is adapted todeliver a pulsed interrogation signal. Response signal sensor 5308 maybe configured to gate detection of the response signal relative to thepulsed interrogation signal. System may include signal processingcircuitry 5320 adapted to process the response signal. In an embodiment,interrogation signal source 5302 is adapted to deliver a pulsedinterrogation signal, and the signal processing circuitry 5320 isconfigured to gate detection of the response signal relative to thepulsed interrogation signal. Signal processing circuitry 5320 may beconfigured to combine multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal, for example, by summing or averaging the multiple responsesignals, or by determining a moving average or weighted sum of themultiple response signals.

In an embodiment, interrogation signal source 5302 is adapted to deliveran interrogation signal containing multiple wavelengths of light. System5300 may include at least a first response signal sensor configured tosense a first response signal produced by the eye of the subjectresponsive to a first wavelength component of the interrogation signal,and a second response signal sensor configured to sense a secondresponse signal produced by the eye of the subject responsive to asecond wavelength component of the interrogation signal (not shown inFIG. 53, but described and depicted elsewhere herein).

In an embodiment, system 5200 includes at least a first interrogationsignal source configured to deliver a first interrogation signal havinga first optical wavelength and at least a second interrogation signalsource configured to deliver a second interrogation signal having asecond optical wavelength. Signal processing circuitry 5320 may beconfigured to process a first response signal sensed from the eye of thesubject in response to the first interrogation signal and a secondresponse signal sensed from the eye of the subject in response to thesecond interrogation signal by comparing the first and second responsesignals to determine the physiological parameter. System may beconfigured to deliver the first interrogation signal simultaneously withrespect to the second interrogation signal, or sequentially with respectto the second interrogation signal.

Interrogation signal source 5302 and the response signal sensor 5308 canbe co-aligned, or separately aligned and located, as described hereinabove.

Output structure 1320 may include various structures, for example, adata transmission structure 1360, serial port 1362, parallel port 1364,electromagnetic transmission means 1366, optical transmission means1368, an audio output 1370, or visual output 1372. Output structure maybe adapted to transmit an output signal to the display. Output structure1320 may be adapted to transmit an output signal to a data processingdevice, and the display may be controlled by the data processing device,for example. For example, such a display may be configured to displayinformation relating to the determined physiological parameter. Adisplay to which housing 1302 is attached via mounting means 1324 may bea video monitor, computer display, video game display, telephonedisplay, or terminal of a data processing device. The display may beincorporated in a wearable item, an article of furniture, an article ofmedical or health-care related equipment, an article of exerciseequipment, or a vehicle. Examples of such displays are described ingreater detail herein above.

In an embodiment, response signal 5308 is indicative of a feature of thevasculature of the eye of the subject. In an embodiment, the responsesignal may be indicative of a biometric identification of the subject.In an aspect, gaze attractor 5120 includes a visual stimulus source fordelivering a visual stimulus to attract the gaze of the subject, asdiscussed herein above. Visual stimulus source may be a mirror, lightsource, or video display, for example. In an aspect, visual stimulussource is adapted for attachment to a video display. In an aspect,visual stimulus source is adapted to produce a visual stimulus thatdiffers from a visual background, e.g., that includes a different lightintensity, different optical wavelength, different temporal pattern oflight intensity, different temporal pattern of optical wavelength,different spatial pattern of light intensity, or different spatialpattern of optical wavelength relative to a visual background. Invarious embodiments, visual stimulus source is adapted to produce avisual stimulus that includes an image, a moving image, or text. In anaspect, visual stimulus source is configured such that when the gaze ofthe subject is directed toward the visual stimulus the eye of thesubject will be brought into alignment with respect to the at least oneof the interrogation signal source 5302 or the response signal sensor5308. In an aspect, gaze attractor 5120 includes at least one auditorystimulus source for delivering a localized auditory stimulus to attractthe gaze of the subject, as discussed herein above. In an aspect, the atleast one auditory stimulus source is configured such that when the gazeof the subject is directed toward the auditory stimulus the eye of thesubject will be brought into alignment with respect to the at least oneof the interrogation signal source 5302 or the response signal sensor5308. In an aspect, gaze attractor 5120 includes at least one auditorystimulus source and at least one visual stimulus source configured todeliver at least one auditory stimulus and at least one visual stimulusin sequence. Gaze attractor 5120 may include at least one auditorystimulus source and at least one visual stimulus source configured todeliver at least one auditory stimulus and at least one visual stimulussimultaneously.

FIG. 54 is a flow chart of a method 5400 of measuring information froman eye of a subject, including delivering an interrogation signal to theeye of the subject with an interrogation signal source 5402; detecting aresponse signal from the eye of the subject with a response signalsensor 5404; controlling a gaze attractor to cause the eye of thesubject to move into alignment with at least one of the interrogationsignal source and the response signal sensor 5406; and determining aphysiological parameter of the subject from the response signal detectedfrom the eye of the subject when the eye of the subject is in alignmentwith respect to the at least one of the interrogation signal source andthe response signal sensor 5408.

FIG. 55 illustrates a further method 5500, which includes detecting agaze signal containing information indicative of a gaze direction of theeye of the subject sensed from at least an eye of the subject 5502;determining the gaze direction of the eye of the subject based upon thegaze signal 5504; and determining whether the eye of the subject is inalignment with respect to at least one of the interrogation signalsource and the response signal sensor based at least in part upon thegaze direction 5506.

In an aspect, method 5500 (and other related methods) may includedelivering a gaze tracking stimulus with a gaze tracking stimulussource, wherein the gaze tracking stimulus is adapted to causeproduction of the gaze signal by the eye of the subject 5508. The methodmay include delivering a gaze tracking stimulus with a plurality of gazetracking stimulus sources 5510. In an embodiment, the method may includedetecting the gaze signal from at least an eye of the subject with acamera 5512, or detecting a plurality of gaze signals containinginformation indicative of the gaze direction of the eye of the subjectfrom at least an eye of the subject 5514. In an aspect, the gaze signaland the response signal are the same signal 5516. Alternatively, thegaze signal and the response signal may be the separate signals 5518.

As shown in FIG. 56, in an embodiment, a method 5600 includesdetermining a feature of the vasculature of the eye of the subject 5602.In an embodiment, method 5600 includes determining a biometricidentification of the subject 5604.

In an embodiment, in a method 5700 depicted in FIG. 57, controlling thegaze attractor includes driving a visual stimulus source to attract thegaze of the subject 5702, such as a mirror 5704, a light source 5706, ora video display 5708 to deliver a visual stimulus. Controlling the gazeattractor can include driving the visual stimulus source to produce avisual stimulus that includes a different light intensity 5710,different optical wavelength 5712, different temporal pattern of lightintensity 5714, different temporal pattern of optical wavelength 5716,different spatial pattern of light intensity 5718, or different spatialpattern of optical wavelength 5720 relative to a visual background.Controlling the gaze attractor can include driving the visual stimulussource to produce a visual stimulus that includes an image 5722, amoving image 5724, or text 5726. Controlling the gaze attractor caninclude driving at least one auditory stimulus source to deliver alocalized auditory stimulus to attract the gaze of the subject 5728. Inan embodiment, controlling the gaze attractor includes driving at leastone auditory stimulus source and at least one visual stimulus source todeliver at least one auditory stimulus and at least one visual stimulusin sequence 5730. In an embodiment, controlling the gaze attractorincludes driving at least one auditory stimulus source and at least onevisual stimulus source to deliver at least one auditory stimulus and atleast one visual stimulus simultaneously 5732.

As shown in FIG. 58, a method 5800 includes determining thephysiological parameter from the response signal detected from aninterior of the eye of the subject responsive to the interrogationsignal 5802, e.g., from a lens 5804, aqueous humor 5806, vitreous humor5808, or retina 5810 of the eye of the subject responsive to theinterrogation signal.

As shown in FIG. 59, in a method 5900, detecting a response signal fromthe eye of the subject includes detecting a first response signal fromthe eye of the subject at a first polarization, determining a secondresponse signal from the eye of the subject at a second polarization,and comparing the response signal determined at the first polarizationto the response signal determined at the second polarization 5902.Depending upon the intended application, the first polarization and thesecond polarization may be different as shown at 5904, or the same asshown at 5906. In an embodiment, delivering the interrogation signalincludes delivering a pulsed interrogation signal 5908. The method mayfurther include gating detection of the response signal relative to thepulsed interrogation signal 5910. In an embodiment, the method includescombining multiple response signals produced by the eye of the subjectin response to multiple pulses of the pulsed interrogation signal 5912.The method may include combining the multiple response signals bysumming 5914 or averaging 5916 the multiple response signals, or bydetermining a moving average 5918 or weighted sum 5920 of the multipleresponse signals.

A shown in FIG. 60, in an embodiment, method 6000 includes delivering afirst interrogation signal having a first optical wavelength to the eyeof the subject and delivering a second interrogation signal having asecond optical wavelength to the eye of the subject 6002. The method mayalso include detecting a first response signal from the eye of thesubject in response to the first interrogation signal and detecting asecond response signal from the eye of the subject in response to thesecond, wherein determining the physiological parameter of the subjectincludes comparing the first response signal and the second responsesignal 6004. For example, it may include delivering the firstinterrogation signal simultaneously with respect to the secondinterrogation signal 6006, or delivering the first interrogation signalsequentially with respect to the second interrogation signal 6008.

As shown in FIG. 61, in an embodiment, a method 6100 includes sending anoutput signal relating to the determined physiological parameter to anoutput structure 6102, which may be, for example, a data transmissionstructure 6104, data storage structure 6106, display 6108, audio output6110, or visual output 6112. As described elsewhere herein, thephysiological parameter determined at step 5408 may be, for example, ameasurement of a substance in the blood of the subject 6114, ameasurement of a substance in an aqueous humor of the subject 6116,oxygen 6118, glucose 6120, a salt 6122, a protein 6124, a lipid 6126, agas 6128, a hormone 6130, a drug 6132, a pulse rate 6134, a blood flow6136, or a temperature 6138.

As shown in FIG. 62, in an aspect, a method 6200 includes reportinginformation regarding the physiological parameter to an interested party6202, such as one or more of the subject, a medical service provider, afamily member, a legal guardian or a legal representative 6204. In anaspect, method 6200 includes comparing the physiological parameterdetermined from the response signal to a previous measurement of aphysiological parameter to determine a physiological trend 6206. Themethod may further include reporting information regarding thephysiological trend to an interested party 6208, such as one or more ofthe subject, a medical service provider, a family member, a legalguardian or a legal representative 6210. In an aspect, method 6200includes utilizing the physiological parameter determined from theresponse signal to assess an emotional state 6212 or the alertness 6214of the subject. In an aspect, the method includes utilizing thephysiological parameter determined from the response signal in a medicalor health-related application 6216. In another aspect, the methodincludes utilizing the physiological parameter determined from theresponse signal in a business or security application 6218.

As shown in FIG. 63, in an embodiment, a method 6300 includes presentingan input to the subject 6302; and utilizing the physiological parameterdetermined from the response signal to determine a response of thesubject to the input 6304. For example, the input may includeinformation 6306 (e.g., advertising information 6308, marketing researchinformation 6310, print information 6312, or video information 6314), anauditory stimulus 6316, a visual stimulus 6318, a tactile stimulus 6320,an olfactory stimulus 6322, a gustatory stimulus 6324, a thermalstimulus 6326, a neural stimulus 6328, a drug 6330, a pharmaceutical6332, a nutraceutical 6334, or a nutrient 6336.

As shown in FIG. 64, in aspect of a method 6400, delivering aninterrogation signal to the eye of the subject with an interrogationsignal source and detecting a response signal from the eye of thesubject with a response signal sensor are performed unobtrusively 6402,or without detection by the subject 6404, as discussed herein above.Method 6400 may also include receiving an input indicative of aninstruction from the subject or representative of the subject forinformation to be measured 6406, receiving an input indicative ofauthorization from the subject or representative of the subject forinformation to be measured 6408, or receiving an input indicative ofinformed consent from the subject or representative of the subject forinformation to be measured 6410.

As shown in FIG. 65, a method may 6500 may include transmitting at leastone of information regarding the subject, information regarding themethod used for determining the physiological parameter, or informationregarding the physiological parameter to a data processing system 6502,receiving at least one of information regarding the subject, informationregarding the method used for determining the physiological parameter,or information regarding the physiological parameter from a dataprocessing system 6504, or sharing at least one of information regardingthe subject, information regarding the method used for determining thephysiological parameter, or information regarding the physiologicalparameter between two of more data processing systems 6506. In anembodiment, method include determining the identity of the subject 6508,for example, through the use of facial recognition 6510, through the useof retinal recognition 6512, or by comparing login information enteredby the subject with login information in a registry 6514. In anembodiment, the method includes controlling the gaze attractor to causethe eye of the subject to move into alignment with the at least one ofthe interrogation signal source and the response signal sensor only whenthe identity of the subject meets a selection criterion. Determiningwhether the identify of the subject meets a selection critereion isperformed generally as discussed herein above, e.g. in connection withFIG. 20.

FIG. 66 depicts an article of manufacture 6600 including one or morenon-transitory machine-readable data storage media 6602 bearing one ormore instructions 6604 for: delivering an interrogation signal to theeye of the subject with an interrogation signal source; detecting aresponse signal from the eye of the subject with a response signalsensor; controlling a gaze attractor to cause the eye of the subject tomove into alignment with at least one of the interrogation signal sourceand the response signal sensor; and determining a physiologicalparameter of the subject from the response signal detected from the eyeof the subject when the eye of the subject is in alignment with respectto the at least one of the interrogation signal source and the responsesignal sensor, e.g., a method as shown in FIG. 54.

In an embodiment, data storage media 6602 may bear one or moreinstructions for detecting a gaze signal containing informationindicative of a gaze direction of the eye of the subject sensed from atleast an eye of the subject; and determining the gaze direction of theeye of the subject based upon the gaze signal; determining whether theeye of the subject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the gaze direction, e.g., as in FIG. 55.

In an embodiment, data storage media 6602 may bear one or moreinstructions for determining a feature of the vasculature of the eye ofthe subject or determining a biometric identification of the subject,e.g. as in FIG. 56.

In an embodiment, data storage media 6602 may bear one or moreinstructions for performing method steps as shown in FIG. 57, e.g. wherethe one or more instructions for controlling the gaze attractor includeone or more instructions for driving a visual stimulus source to delivera visual stimulus (e.g., a mirror, light source, or video display) toattract the gaze of the subject. In various embodiments, the one or moreinstructions for controlling the gaze attractor include one or moreinstructions for driving the visual stimulus source to produce a visualstimulus that includes a different light intensity, a different opticalwavelength, a different temporal pattern of light intensity, a differenttemporal pattern of optical wavelength, a different spatial pattern oflight intensity or a different spatial pattern of optical wavelengthrelative to a visual background. In addition, the one or moreinstructions for controlling the gaze attractor may include one or moreinstructions driving the visual stimulus source to produce a visualstimulus that includes an image, a moving image, or text. In anembodiment, the one or more instructions for controlling the gazeattractor include one or more instructions for driving at least oneauditory stimulus source to deliver a localized auditory stimulus toattract the gaze of the subject. In an aspect, the one or moreinstructions for controlling the gaze attractor include one or moreinstructions for driving at least one auditory stimulus source and atleast one visual stimulus source to deliver at least one auditorystimulus and at least one visual stimulus in sequence. In anotheraspect, the one or more instructions for controlling the gaze attractorinclude one or more instructions for driving at least one auditorystimulus source and at least one visual stimulus source to deliver atleast one auditory stimulus and at least one visual stimulussimultaneously.

In an embodiment, the data storage media 6602 bear one or moreinstructions for performing method steps as shown in FIG. 55, includingone or more instructions for delivering a gaze tracking stimulus with agaze tracking stimulus source, wherein the gaze tracking stimulus isadapted to cause production of the gaze signal the eye of the subject,or one or more instructions for delivering a gaze tracking stimulus witha plurality of gaze tracking stimulus sources. In an embodiment, thedata storage media bear one or more instructions for detecting the gazesignal from at least an eye of the subject with a camera. In anembodiment, the data storage media bear one or more instructions fordetecting a plurality of gaze signals containing information indicativeof the gaze direction of the eye of the subject from at least an eye ofthe subject.

In an embodiment, the data storage media 6602 may bear one or moreinstructions for determining the physiological parameter from theresponse signal detected from an interior of the eye (e.g., from a lens,aqueous humor, vitreous humor, or retina) of the subject responsive tothe interrogation signal, e.g. as in the method of FIG. 58.

In an embodiment, data storage media 6602 bear one or more instructionsfor performing method steps as shown in FIG. 59, e.g. where the one ormore instructions for detecting a response signal from the eye of thesubject include one or more instructions for detecting a first responsesignal from the eye of the subject at a first polarization, determininga second response signal from the eye of the subject at a secondpolarization, and comparing the response signal determined at the firstpolarization to the response signal determined at the secondpolarization. The first polarization and the second polarization may bedifferent, or the same as discussed above. In an embodiment, one or moreinstructions for delivering the interrogation signal includes one ormore instructions for delivering a pulsed interrogation signal.

The data storage media may bear one or more instructions for gatingdetection of the response signal relative to the pulsed interrogationsignal. The data storage media may bear one or more instructions forcombining multiple response signals produced by the eye of the subjectin response to multiple pulses of the pulsed interrogation signal, e.g.by summing or averaging the multiple response signals, or by determininga moving average or weighted sum of the multiple response signals.

The data storage media 6002 may bear one or more instructions fordelivering a first interrogation signal having a first opticalwavelength to the eye of the subject and delivering a secondinterrogation signal having a second optical wavelength to the eye ofthe subject, as shown in FIG. 60. In addition, data storage media 6002may bear one or more instructions for detecting a first response signalfrom the eye of the subject in response to the first interrogationsignal and detecting a second response signal from the eye of thesubject in response to the second, wherein determining the physiologicalparameter of the subject includes comparing the first response signaland the second response signal. The data storage media 6002 may bear oneor more instructions for delivering the first interrogation signalsimultaneously with respect to the second interrogation signal. The datastorage media 6002 may bear one or more instructions for delivering thefirst interrogation signal sequentially with respect to the secondinterrogation signal.

The data storage media 6002 may bear one or more instruction forperforming a method as shown in FIG. 61, including one or moreinstructions for sending an output signal relating to the determinedphysiological parameter to an output device, which may be, for example,a data transmission structure, data storage structure, display, audiooutput, or visual output. The physiological parameter may be ameasurement of a substance in the blood of the subject (e.g. oxygen,glucose, or glycosylated hemoglobin), a measurement of a substance in anaqueous humor of the subject (e.g., oxygen, glucose, or glycosylatedhemoglobin), a pulse rate, a temperature, or a blood flow, for example.

In an embodiment, the data storage media 6002 bear one or moreinstructions for performing a method as shown in FIG. 62, including oneor more instructions for comparing the physiological parameterdetermined from the response signal to a previous measurement of aphysiological parameter to determine a physiological trend. In addition,the data storage media may bear one or more instructions for reportinginformation regarding the physiological trend to an interested party(for example, one or more of the subject, a medical service provider, afamily member, a legal guardian or a legal representative). In anaspect, the data storage media 6002 bear one or more instructions forutilizing the physiological parameter determined from the responsesignal to assess an emotional state of the subject. In an aspect, thedata storage media 6002 bear one or more instructions for utilizing thephysiological parameter determined from the response signal to assessthe alertness of the subject. In an aspect, the data storage media 6002bear one or more instructions for utilizing the physiological parameterdetermined from the response signal in a medical or health-relatedapplication. In another aspect, the data storage media 6002 bear one ormore instructions for utilizing the physiological parameter determinedfrom the response signal in a business or security application.

In an aspect, the data storage media 6002 bear one or more instructionsfor performing a method as shown in FIG. 63, including one or moreinstructions for presenting an input to the subject; and utilizing thephysiological parameter determined from the response signal to determinea response of the subject to the input. The one or more instructions forpresenting an input to the subject may include one or more instructionsfor presenting information (e.g., advertising information, marketingresearch information, print information, or video information), orpresenting a stimulus (e.g., an auditory stimulus, visual stimulus,tactile stimulus, olfactory stimulus, gustatory stimulus, thermalstimulus, neural stimulus, drug, pharmaceutical, nutraceutical, ornutrient).

In an aspect, the data storage media 6002 bear one or more instructionsfor methods as shown in FIG. 64, including one or more instructions forreceiving an input indicative of an instruction from the subject orrepresentative of the subject for information to be measured. In anaspect, the data storage media 6002 bear one or more instructions forreceiving an input indicative of authorization from the subject orrepresentative of the subject for information to be measured. In anaspect, the data storage media 6002 bear one or more instructions forreceiving an input indicative of informed consent from the subject orrepresentative of the subject for information to be measured.

In various embodiments, the data storage media 6002 bear one or moreinstructions for performing a method as shown in FIG. 65, including oneor more instructions for transmitting at least one of informationregarding the subject, information regarding the method used fordetermining the physiological parameter, or information regarding thephysiological parameter to a data processing system, receiving at leastone of information regarding the subject, information regarding themethod used for determining the physiological parameter, or informationregarding the physiological parameter from a data processing system, orsharing at least one of information regarding the subject, informationregarding the method used for determining the physiological parameter,or information regarding the physiological parameter between two of moredata processing systems. In an aspect, the data storage media 6002 bearone or more instructions for determining the identity of the subject,for example through the use of facial recognition, through the use ofretinal recognition, or by comparing login information entered by thesubject with login information in a registry.

Although specific embodiments are described herein, those skilled in theart will appreciate that methods and systems as described herein can beimplemented in various ways. FIG. 67 depicts a generic system 6700,illustrating components of systems described herein above. Reference ismade throughout to “signal processing circuitry.” Signal processingcircuitry, as used herein, for example, such as signal processingcircuitry 6702 illustrated in FIG. 67, may include any or all of digitaland/or analog components 6704, one or more processor 6706 (e.g. amicroprocessor), and memory 6708, which may store program module 6710and/or data 6712. Systems as described herein may receive signals fromvarious sensors (e.g., sensors 6714 and 6716 depicted in FIG. 67) andsend control signals to various types of signal sources used forinterrogating the eye to determine eye position or physiologicalparameters (e.g. sources 6718 and 6720). System 6700 may include othercomponents as known to those skilled in the art, e.g. one or more powersupply 6722, and I/O structure 6724. I/O structure permits communicationwith various types of user interface devices (represented by userinterface 6730) and various types of remote device 6732, which may havesignal processing capability conferred by signal processing circuitry6743 and may perform some or all of the signal processing tasks requiredby system 6700, or which may perform additional processing of datagenerated by 6700, e.g. determination of appropriate medical treatmentbased on physiological parameters.

In a general sense, those skilled in the art will recognize that thevarious embodiments described herein can be implemented, individuallyand/or collectively, by various types of electro-mechanical systemshaving a wide range of electrical components such as hardware, software,firmware, and/or virtually any combination thereof, limited topatentable subject matter under 35 U.S.C. §101; and a wide range ofcomponents that may impart mechanical force or motion such as rigidbodies, spring or torsional bodies, hydraulics, electro-magneticallyactuated devices, and/or virtually any combination thereof.Consequently, as used herein “electro-mechanical system” includes, butis not limited to, electrical circuitry operably coupled with atransducer (e.g., an actuator, a motor, a piezoelectric crystal, a MicroElectro Mechanical System (MEMS), etc), electrical circuitry having atleast one discrete electrical circuit, electrical circuitry having atleast one integrated circuit, electrical circuitry having at least oneapplication specific integrated circuit, electrical circuitry forming ageneral purpose computing device configured by a computer program (e.g.,a general purpose computer configured by a computer program which atleast partially carries out processes and/or devices described herein,or a microprocessor configured by a computer program which at leastpartially carries out processes and/or devices described herein),electrical circuitry forming a memory device (e.g., forms of memory(e.g., random access, flash, read only, etc.)), electrical circuitryforming a communications device (e.g., a modem, communications switch,optical-electrical equipment, etc), and/or any non-electrical analogthereto, such as optical or other analogs (e.g., graphene basedcircuitry). Those skilled in the art will also appreciate that examplesof electro-mechanical systems include but are not limited to a varietyof consumer electronics systems, medical devices, as well as othersystems such as motorized transport systems, security systems, and/orcommunication/computing systems. Those skilled in the art will recognizethat electro-mechanical as used herein is not necessarily limited to asystem that has both electrical and mechanical actuation except ascontext may dictate otherwise. In a general sense, those skilled in theart will recognize that the various aspects described herein which canbe implemented, individually and/or collectively, by a wide range ofhardware, software, firmware, and/or any combination thereof can beviewed as being composed of various types of “electrical circuitry.”

Those skilled in the art will recognize that at least a portion of thedevices and/or processes described herein can be integrated into animage processing system. Those having skill in the art will recognizethat a typical image processing system generally includes one or more ofa system unit housing, a video display, memory such as volatile ornon-volatile memory, processors such as microprocessors or digitalsignal processors, computational entities such as operating systems,drivers, applications programs, one or more interaction devices (e.g., atouch pad, a touch screen, an antenna, etc), control systems includingfeedback loops and control motors (e.g., feedback for sensing lensposition and/or velocity; control motors for moving/distorting lenses togive desired focuses). An image processing system may be implementedutilizing suitable commercially available components, such as thosetypically found in digital still systems and/or digital motion systems.

Those skilled in the art will recognize that at least a portion of thedevices and/or processes described herein can be integrated into a dataprocessing system. Those having skill in the art will recognize that adata processing system generally includes one or more of a system unithousing, a video display, memory such as volatile or non-volatilememory, processors such as microprocessors or digital signal processors,computational entities such as operating systems, drivers, graphicaluser interfaces, and applications programs, one or more interactiondevices (e.g., a touch pad, a touch screen, an antenna, etc), and/orcontrol systems including feedback loops and control motors (e.g.,feedback for sensing position and/or velocity; control motors for movingand/or adjusting components and/or quantities). A data processing systemmay be implemented utilizing suitable commercially available components,such as those typically found in data computing/communication and/ornetwork computing/communication systems.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures may beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable,” to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In some instances, one or more components may be referred to herein as“configured to,” “configured by,” “configurable to,” “operable/operativeto,” “adapted/adaptable,” “able to,” “conformable/conformed to,” etc.Those skilled in the art will recognize that such terms (e.g.“configured to”) generally encompass active-state components and/orinactive-state components and/or standby-state components, unlesscontext requires otherwise.

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to those skilled inthe art that, based upon the teachings herein, changes and modificationsmay be made without departing from the subject matter described hereinand its broader aspects and, therefore, the appended claims are toencompass within their scope all such changes and modifications as arewithin the true spirit and scope of the subject matter described herein.It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to claims containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that typically a disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms unless context dictates otherwise. For example, the phrase “Aor B” will be typically understood to include the possibilities of “A”or “B” or “A and B.”

With respect to the appended claims, those skilled in the art willappreciate that recited operations therein may generally be performed inany order. Also, although various operational flows are presented in asequence(s), it should be understood that the various operations may beperformed in other orders than those which are illustrated, or may beperformed concurrently. Examples of such alternate orderings may includeoverlapping, interleaved, interrupted, reordered, incremental,preparatory, supplemental, simultaneous, reverse, or other variantorderings, unless context dictates otherwise. Furthermore, terms like“responsive to,” “related to,” or other past-tense adjectives aregenerally not intended to exclude such variants, unless context dictatesotherwise.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

What is claimed is:
 1. A system for sensing information from an eye of asubject, comprising: a gaze signal sensor adapted for receiving a gazesignal containing information indicative of a gaze direction of the eyeof the subject; an interrogation signal source for delivering theinterrogation signal to the eye of the subject; a response signal sensorfor sensing a response signal produced by the eye of the subjectresponsive to the interrogation signal; and signal processing circuitryincluding: a gaze signal processor configured to determine the gazedirection of the eye of the subject based upon the gaze signal; analignment detector configured to determine whether the eye of thesubject is in alignment with respect to at least one of theinterrogation signal source and the response signal sensor based atleast in part upon the gaze direction; and a response signal processorconfigured to process the response signal sensed from the eye of thesubject by the response signal sensor when the eye of the subject is inalignment with respect to the at least one of the interrogation signalsource and the response signal sensor to determine a physiologicalparameter from the response signal.
 2. A system for controlling thesensing of information from an eye of a subject, comprising: signalprocessing circuitry including: a gaze signal input adapted to receive agaze signal containing information indicative of a gaze direction of theeye of the subject sensed from at least the eye of the subject; aresponse signal input adapted to receive a response signal sensed fromthe eye of the subject by a response signal sensor responsive todelivery of an interrogation signal to the eye of the subject; a gazesignal processor configured to determine the gaze direction of the eyeof the subject based upon the gaze signal; an alignment detectorconfigured to determine whether the eye of the subject is in alignmentwith respect to at least one of the interrogation signal source and theresponse signal sensor based at least in part upon the gaze direction;and a response signal processor configured to process the responsesignal sensed from the eye of the subject by the response signal sensorwhen the eye of the subject is in alignment with respect to the at leastone of the interrogation signal source and the response signal sensor todetermine a physiological parameter from the response signal.
 3. Thesystem of claim 1, wherein the gaze signal sensor includes at least oneof a camera, an infrared camera, a CCD camera, an optical sensor, and anoptical sensor array.
 4. The system of claim 1, wherein theinterrogation signal source includes at least one of an optical signalsource, an acoustic signal source, a broad spectrum light source, anear-infrared light source, a tunable laser source, and a mid-infraredlight source.
 5. The system of claim 1, wherein the response signalsensor includes at least one of an optical sensor, an acoustic sensor, aspectrometer based on a CCD array, a near-infrared camera, a Ramanspectrometer based on a CCD camera, a mid-infrared detector, and a broadspectrum pyroelectric detector.
 6. The system of claim 1, including atleast one gaze tracking stimulus source adapted to deliver a gazetracking stimulus to at least the eye of the subject, wherein the gazesignal is produced in response to the gaze tracking stimulus, andwherein the gaze tracking stimulus source includes at least one of aninfra-red source and a near infra-red source.
 7. The system of claim 1,wherein the interrogation signal source is adapted to deliver a pulsedinterrogation signal, and wherein the signal processing circuitry isconfigured to combine multiple response signals produced by the eye ofthe subject in response to multiple pulses of the pulsed interrogationsignal by at least one of summing the multiple response signals,averaging the multiple response signals, determining a moving average ofthe multiple response signals, and determining a weighted sum of themultiple response signals.
 8. The system of claim 1, including at leasta first response signal sensor, and a second response signal sensor,wherein the interrogation signal source is adapted to deliver aninterrogation signal containing multiple wavelengths of light, andwherein the first response signal sensor is configured to sense a firstresponse signal produced by the eye of the subject responsive to a firstwavelength component of the interrogation signal, and the secondresponse signal sensor is configured to sense a second response signalproduced by the eye of the subject responsive to a second wavelengthcomponent of the interrogation signal.
 9. The system of claim 1,including at least a first interrogation signal source configured todeliver a first interrogation signal having a first optical wavelengthand at least a second interrogation signal source configured to delivera second interrogation signal having a second optical wavelength,wherein the signal processing circuitry is configured to process a firstresponse signal sensed from the eye of the subject in response to thefirst interrogation signal and a second response signal sensed from theeye of the subject in response to the second interrogation signal bycomparing the first and second response signals to determine thephysiological parameter.
 10. The system of claim 1, including at leastone of an output structure adapted to output a signal relating to thedetermined physiological parameter and a display adapted to displayinformation relating to the determined physiological parameter.
 11. Thesystem of claim 10, wherein the output structure includes at least oneof a data transmission structure, a data storage structure, a display,an audio output, and a visual output.
 12. The system of claim 10,wherein the display includes at least one of a video monitor, a computerdisplay, a video game display, a telephone display, a terminal of a dataprocessing device, a display incorporated in a wearable item, a displayincorporated in an article of furniture, a display incorporated in anarticle of medical or health-care related equipment, a displayincorporated in an article of exercise equipment and a displayincorporated in a vehicle.
 13. The system of claim 2, including:interrogation signal control circuitry configured to drive production ofthe interrogation signal by an interrogation signal source; and gazetracking stimulus control circuitry configured to drive production of agaze tracking stimulus by at least one gaze tracking stimulus source.14. The system of claim 2, wherein the response signal processor isconfigured to process the response signal sensed from the eye of thesubject by the response signal sensor when the eye of the subject is inalignment with respect to the at least one of the interrogation signalsource and the response signal sensor to determine a measurement of atleast one of oxygenation, blood glucose, a heart rate, glycosylatedhemoglobin, a temperature, a body temperature, a blood flow, and asubstance in the eye of the subject from the response signal.
 15. Thesystem of claim 2, including interrogation control circuitry configuredto drive production of a pulsed interrogation signal by an interrogationsignal source, and wherein the signal processing circuitry is configuredto gate detection of the response signal relative to the pulsedinterrogation signal.
 16. The system of claim 2, including interrogationcontrol circuitry configured to drive production of a pulsedinterrogation signal by an interrogation signal source, and wherein thesignal processing circuitry is configured to combine multiple responsesignals produced by the eye of the subject in response to multiplepulses of the pulsed interrogation signal by at least one of summing themultiple response signals, averaging the multiple response signals,determining a moving average of the multiple response signals, anddetermining a weighted sum of the multiple response signals.
 17. Thesystem of claim 2, including at least one of an output structure adaptedto output a signal relating to the determined physiological parameterand a display adapted to display information relating to the determinedphysiological parameter.
 18. The system of claim 1, wherein theinterrogation signal source is adapted to produce light having a firstpolarization, wherein the response signal sensor is adapted to detectlight having a second polarization, and where the first polarization andthe second polarization are different.
 19. The system of claim 1,wherein the interrogation signal source is adapted to produce lighthaving a first polarization, wherein the response signal sensor isadapted to detect light having a second polarization, and where thefirst polarization and the second polarization are the same.
 20. Thesystem of claim 1, wherein interrogation signal source and the responsesignal sensor are separately co-aligned.
 21. The system of claim 1,wherein interrogation signal source and the response signal sensor areseparately aligned and located.
 22. The system of claim 2, includinggaze tracking stimulus control circuitry configured to drive productionof a gaze tracking stimulus by a plurality of gaze tracking stimulussources.
 23. The system of claim 2, including interrogation signalcontrol circuitry configured to drive production of a firstinterrogation signal having a first optical wavelength and production ofa second interrogation signal having a second optical wavelength.